Dataset Information

Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in children with DEND-associated mutations and may be improved by early treatment with sulfonylureas.

ABSTRACT:

Objective

To assess performance on an age-standardized neuromotor coordination task among sulfonylurea-treated KCNJ11-related neonatal diabetic patients.

Research design and methods

Nineteen children carrying KCNJ11 mutations associated with isolated diabetes (R201H; n = 8), diabetes with neurodevelopmental impairment (V59M or V59A [V59M/A]; n = 8), or diabetes not consistently associated with neurodevelopmental disability (Y330C, E322K, or R201C; n = 3) were studied using the age-standardized Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI).

Results

Although R201H subjects tested in the normal range (median standard score = 107), children with V59M/A mutations had significantly lower than expected VMI standard scores (median = 49). The scores for all three groups were significantly different from each other (P = 0.0017). The age of sulfonylurea initiation was inversely correlated with VMI scores in the V59M/A group (P < 0.05).

Conclusions

Neurodevelopmental disability in KCNJ11-related diabetes includes visuomotor problems that may be ameliorated by early sulfonylurea treatment. Comprehensive longitudinal assessment on larger samples will be imperative.

SUBMITTER: Shah RP

PROVIDER: S-EPMC3447845 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Publications

Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in children with DEND-associated mutations and may be improved by early treatment with sulfonylureas.

Shah Reshma P RP Spruyt Karen K Kragie Brigette C BC Greeley Siri Atma W SA Msall Michael E ME

Diabetes care 20120801 10

<h4>Objective</h4>To assess performance on an age-standardized neuromotor coordination task among sulfonylurea-treated KCNJ11-related neonatal diabetic patients.<h4>Research design and methods</h4>Nineteen children carrying KCNJ11 mutations associated with isolated diabetes (R201H; n = 8), diabetes with neurodevelopmental impairment (V59M or V59A [V59M/A]; n = 8), or diabetes not consistently associated with neurodevelopmental disability (Y330C, E322K, or R201C; n = 3) were studied using the age ...[more]

PMID: 22855734

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Project description:Aims/hypothesisThe finding that patients with diabetes due to potassium channel mutations can transfer from insulin to sulfonylureas has revolutionised the management of patients with permanent neonatal diabetes. The extent to which the in vitro characteristics of the mutation can predict a successful transfer is not known. Our aim was to identify factors associated with successful transfer from insulin to sulfonylureas in patients with permanent neonatal diabetes due to mutations in KCNJ11 (which encodes the inwardly rectifying potassium channel Kir6.2).MethodsWe retrospectively analysed clinical data on 127 patients with neonatal diabetes due to KCNJ11 mutations who attempted to transfer to sulfonylureas. We considered transfer successful when patients completely discontinued insulin whilst on sulfonylureas. All unsuccessful transfers received ≥0.8 mg kg(-1) day(-1) glibenclamide (or the equivalent) for >4 weeks. The in vitro response of mutant Kir6.2/SUR1 channels to tolbutamide was assessed in Xenopus oocytes. For some specific mutations, not all individuals carrying the mutation were able to transfer successfully; we therefore investigated which clinical features could predict a successful transfer.ResultsIn all, 112 out of 127 (88%) patients successfully transferred to sulfonylureas from insulin with an improvement in HbA1c from 8.2% (66 mmol/mol) on insulin, to 5.9% (41 mmol/mol) on sulphonylureas (p = 0.001). The in vitro response of the mutation to tolbutamide determined the likelihood of transfer: the extent of tolbutamide block was <63% for the p.C166Y, p.I296L, p.L164P or p.T293N mutations, and no patients with these mutations successfully transferred. However, most individuals with mutations for which tolbutamide block was >73% did transfer successfully. The few patients with these mutations who could not transfer had a longer duration of diabetes than those who transferred successfully (18.2 vs 3.4 years, p = 0.032). There was no difference in pre-transfer HbA1c (p = 0.87), weight-for-age z scores (SD score; p = 0.12) or sex (p = 0.17).Conclusions/interpretationTransfer from insulin is successful for most KCNJ11 patients and is best predicted by the in vitro response of the specific mutation and the duration of diabetes. Knowledge of the specific mutation and of diabetes duration can help predict whether successful transfer to sulfonylureas is likely. This result supports the early genetic testing and early treatment of patients with neonatal diabetes aged under 6 months.

Dataset Information

Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in children with DEND-associated mutations and may be improved by early treatment with sulfonylureas.

Objective

Research design and methods

Results

Conclusions

Publications

Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in children with DEND-associated mutations and may be improved by early treatment with sulfonylureas.

Similar Datasets

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