Aetiology of transient neonatal diabetes.

Milner, R. D. G.; Ferguson, Amy; Naidu, S.

doi:10.1136/adc.46.249.724

Cited by 37 publications

(3 citation statements)

References 7 publications

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“…We ascertained 30 patients who fulfilled the criteria. Of these, 23 were sporadic cases (including 1 set of identical twins), and 7 were familial (3 from 1 family [29] and 4 from the other [30,31]). The clinical and molecular details are shown in Table 3.…”

Section: Resultsmentioning

confidence: 99%

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

et al. 2000

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Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon after birth, resolves by 18 months, and predisposes to diabetes later in life. A total of 30 patients were ascertained and investigated for aberrations of chromosome 6. A genotype/phenotype study was also performed. Genotypically, these patients can be classified into 4 etiologic groups. Group 1 had paternal uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical twins). Group 2 had a duplication involving chromosome band 6q24, which was paternal in origin where tested (4 sporadic cases and 7 familial cases from 2 families). Group 3 consisted of 1 patient with a loss of methylation at a CpG island within the TND critical region (1 sporadic case). Group 4 had no identifiable rearrangement of chromosome 6 (7 sporadic cases). Most patients were growth retarded at birth, presented at a median age of 3 days, and recovered at a median age of 12 weeks. In group 2, 2 relatives of the TND patients who presented with type 2 diabetes and no early history of TND had inherited an identical duplication. An abnormality of chromosome 6 was identified in approximately 70% of sporadic TND cases and in all familial cases. No significant clinical differences were found between the 4 etiological groups. The study has broadened the clinical spectrum of TND to include type 2 diabetes presenting in later life with no neonatal presentation. The findings are consistent with an imprinted gene for diabetes mapping to 6q24, which we predict will have an important function in normal pancreatic development.

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Section: Resultsmentioning

confidence: 99%

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

et al. 2000

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“…Urinary insulin excretion de clined significantly, suggesting that at least part of the long-term effect of tolbutamide was mediated through beta cell stimulation. By measuring urine insulin during the first week of life, M iln er et al [86] were able to show that transient neonatal diabetes was associated with insulin deficiency, most probably related to a delay in the functional maturation of the fetal beta cells. It is of interest that C rossley and E llio tt [28] have suggested that a high proportion of proinsulin-like material may be present in the urine of un treated juvenile onset diabetics and further studies to confirm and quantitate this observation are now needed.…”

Section: Excretionmentioning

confidence: 99%

Insulin and the Kidney

Rubenstein

Mako

Horwitz

1975

Nephron

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Changes in renal function and structure are frequently observed in patients with diabetes mellitus. In the early phases of the disease, alterations in glomerular filtration rate, renal plasma flow, glomerular permeability and tubular capacity for glucose reabsorption occur. In the late stages of juvenile onset diabetes, renal failure is a common cause of death. For this reason, increasing attention is being paid to the possibility of long-term dialysis and renal transplantation in these patients. The kidneys play an important role in regulating insulin metabolism. The renal arteriovenous difference is approximately 30–45% and a linear relationship exists between the arterial insulin level and the renal arteriovenous concentration difference. The renal extraction of insulin is 200 ml/min in man, and it is estimated that 6–8 U are removed and degraded by the kidney in 24 h. The quantity of insulin in urine is small. However, its clearance is relatively constant over a wide range of serum concentrations and is 0.15–0.5 ml/min. The mean basal insulin excretion is 3.6 µU/mg creatinine, and a fourfold rise occurs following a glucose load. The urinary insulin values in neonates, children and patients with diabetes and renal failure are reviewed. In diabetic patients, progressive renal disease is accompanied by decreasing insulin requirements. In contrast, nondiabetic patients who develop renal failure frequently show abnormalities in carbohydrate metabolism, the commonest of which is a pseudodiabetic state.

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“…1 TNDM is a rare genetic form of diabetes. It is a developmental disease of insulin production (5) predicted to arise from a defect in pancreatic ␤-cell maturation (6,7). Most TNDM cases are sporadic, but familial cases also exist.…”

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confidence: 99%

Characterization of the Methylation-sensitive Promoter of the Imprinted ZAC Gene Supports Its Role in Transient Neonatal Diabetes Mellitus

Varrault

Bilanges

Mackay

et al. 2001

Journal of Biological Chemistry

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ZAC is a recently isolated zinc finger protein that induces apoptosis and cell cycle arrest. The corresponding gene is imprinted maternally through an unknown mechanism and maps to 6q24 -q25, within the minimal interval harboring the gene responsible for transient neonatal diabetes mellitus (TNDM) and a tumor suppressor gene involved in breast cancer. Because of its functional properties, imprinting status, and expression pattern in mammary cell lines and tumors, ZAC is the best candidate so far for both disease conditions. In the present work, we delineated ZAC genomic organization and mapped its transcriptional start site. It is noteworthy that the ZAC promoter localized to the CpG island harboring the methylation imprint associated with TNDM and methylation of this promoter silenced its activity. These data indicate that the methylation mark may have a direct effect on the silencing of the ZAC imprinted allele. Our findings further strengthen the hypothesis that ZAC is the gene responsible for TNDM and suggest a novel mechanism for ZAC inactivation in breast tumors.

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Aetiology of transient neonatal diabetes.

Cited by 37 publications

References 7 publications

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.

Insulin and the Kidney

Characterization of the Methylation-sensitive Promoter of the Imprinted ZAC Gene Supports Its Role in Transient Neonatal Diabetes Mellitus

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