Sulfonylurea Treatment in Young Children With Neonatal Diabetes

Codner, Ethel; Flanagan, Sarah E.; Ugarte, Francisca; García, H; Vidal, Teresa; Ellard, Sian; Hattersley, Andrew T.

doi:10.2337/dc06-2134

Cited by 30 publications

(27 citation statements)

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“…One patient had mild transitory diarrhea on glyburide, which has been previously reported (15), but when transferred to tolbutamide, another sulfonylurea, no further side effects were experienced. Another patient had morning nausea while on glyburide, which may have been a side effect of the sulfonylurea therapy but resolved without discontinuing treatment.…”

Section: Side Effectssupporting

confidence: 53%

“…Successful transfer from insulin to oral sulfonylureas has been described in eight patients with neonatal diabetes due to SUR1 mutations (9,10,(15)(16)(17). This study will examine the treatment response to sulfonylureas in a cohort of 27 patients with diabetes due to SUR1 mutations to identify whether they can be used effectively and how their transfer and treatment differ from that in Kir6.2 patients.…”

mentioning

confidence: 99%

“…The observation period was at least 2 months after commencing sulfonylureas in all patients. Treatment details for two patients have been described previously (8,15,17).…”

mentioning

confidence: 99%

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Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

et al. 2008

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OBJECTIVE -Neonatal diabetes can result from mutations in the Kir6.2 or sulfonylurea receptor 1 (SUR1) subunits of the ATP-sensitive K ϩ channel. Transfer from insulin to oral sulfonylureas in patients with neonatal diabetes due to Kir6.2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and to compare it with Kir6.2 mutations.RESEARCH DESIGN AND METHODS -We followed 27 patients with SUR1 mutations for at least 2 months after attempted transfer to sulfonylureas. Information was collected on clinical features, treatment before and after transfer, and the transfer protocol used. We compared successful and unsuccessful transfer patients, glycemic control before and after transfer, and treatment requirements in patients with SUR1 and Kir6.2 mutations. RESULTS -Twenty-three patients (85%) successfully transferred onto sulfonylureas without significant side effects or increased hypoglycemia and did not need insulin injections. In these patients, median A1C fell from 7.2% (interquartile range 6.6 -8.2%) on insulin to 5.5% (5.3-6.2%) on sulfonylureas (P ϭ 0.01). When compared with Kir6.2 patients, SUR1 patients needed lower doses of both insulin before transfer (0.4 vs. 0.7 units ⅐ kg Ϫ1 ⅐ day Ϫ1 ; P ϭ 0.002) and sulfonylureas after transfer (0.26 vs. 0.45 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ; P ϭ 0.005).CONCLUSIONS -Oral sulfonylurea therapy is safe and effective in the short term in most patients with diabetes due to SUR1 mutations and may successfully replace treatment with insulin injections. A different treatment protocol needs to be developed for this group because they require lower doses of sulfonylureas than required by Kir6.2 patients.

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Section: Side Effectssupporting

confidence: 53%

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confidence: 99%

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Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

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“…ABCC8 mutations have been reported previously in 39 index cases with neonatal diabetes [13][14][15][16][17][18]. In this article, we describe a further nine families (figure 1) bringing the total number to 48 (table 1).…”

Section: Abcc8 Mutations Causing Diabetes Mellitusmentioning

confidence: 78%

“…Activating mutations in KCNJ11 are now known to cause both PNDM and TNDM in humans [6,7]. ABCC8 was therefore an excellent candidate gene for neonatal diabetes, and during the past year, several reports have described activating mutations in the ABCC8 gene in patients with PNDM or TNDM [13][14][15][16][17][18].…”

Section: Abcc8 As a Candidate Gene For Neonatal Diabetesmentioning

confidence: 99%

Mutations in the ABCC8 gene encoding the SUR1 subunit of the K_ATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period

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et al. 2007

Diabetes Obesity Metabolism

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Aim: Mutations in the ABCC8 gene encoding the SUR1 subunit of the pancreatic ATP‐sensitive potassium channel cause permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We reviewed the existing literature, extended the number of cases and explored genotype–phenotype correlations. Methods: Mutations were identified by sequencing in patients diagnosed with diabetes before 6 months without a KCNJ11 mutation. Results: We identified ABCC8 mutations in an additional nine probands (including five novel mutations L135P, R306H, R1314H, L438F and M1290V), bringing the total of reported families to 48. Both dominant and recessive mutations were observed with recessive inheritance more common in PNDM than TNDM (9 vs. 1; p < 0.01). The remainder of the PNDM probands (n = 12) had de novo mutations. Seventeen of twenty‐five children with TNDM inherited their heterozygous mutation from a parent. Nine of these parents had permanent diabetes (median age at diagnosis: 27.5 years, range: 13–35 years). Recurrent mutations of residues R1183 and R1380 were found only in TNDM probands and dominant mutations causing PNDM clustered within exons 2–5. Conclusions: ABCC8 mutations cause PNDM, TNDM or permanent diabetes diagnosed outside the neonatal period. There is some evidence that the location of the mutation is correlated with the clinical phenotype.

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Update of mutations in the genes encoding the pancreatic beta-cell K_ATPchannel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism

et al. 2008

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ABSTRACT:The beta-cell ATP-sensitive potassium (K ATP ) channel is a key component of stimulus-secretion coupling in the pancreatic beta-cell. The channel couples metabolism to membrane electrical events bringing about insulin secretion. Given the critical role of this channel in glucose homeostasis it is therefore not surprising that mutations in the genes encoding for the two essential subunits of the channel can result in both hypo-and hyperglycemia. The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1). It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes. This review focuses on reported mutations in both genes, the spectrum of phenotypes, and the implications for treatment on diagnosing patients with mutations in these genes.

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Sulfonylurea Treatment in Young Children With Neonatal Diabetes

Cited by 30 publications

References 7 publications

Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

Mutations in the ABCC8 gene encoding the SUR1 subunit of the K_ATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period

Update of mutations in the genes encoding the pancreatic beta-cell K_ATPchannel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism

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Sulfonylurea Treatment in Young Children With Neonatal Diabetes

Cited by 30 publications

References 7 publications

Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

Mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period

Update of mutations in the genes encoding the pancreatic beta-cell KATPchannel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism

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Mutations in the ABCC8 gene encoding the SUR1 subunit of the K_ATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period

Update of mutations in the genes encoding the pancreatic beta-cell K_ATPchannel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism