You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
neonatal diabetes , defined as insulin - requiring hyperglycemia within the first three months of life , is a rare disease entity , with an estimated incidence of 1 in 400,000 neonates ( 1 ) .
transient neonatal diabetes usually resolves by a median of 12 weeks and is generally associated with an abnormality of the imprinted region of 6q24 ( 2 ) . by contrast ,
permanent neonatal diabetes ( pnd ) requires insulin treatment for life , and until recently the genetic etiology was largely unknown .
recently , gloyn et al . ( 3 ) reported that heterozygous activating mutations in the kcnj11 gene are a common cause of pnd . kcnj11
encodes kir6.2 , the pore - forming subunit of the atp - sensitive k channel ( katp channel ) ( 4 ) .
katp channels play a central role in glucose - stimulated insulin secretion from pancreatic -cells ( 5 ) .
sulfonylurea stimulates insulin secretion by binding to the -cell 's high - affinity sulfonylurea receptor and closing the atp - sensitive k+ channels by an atp - independent mechanism ( 6 ) .
( 7 ) recently reported that oral sulfonylurea should be considered for treatment of patients with kir6.2 mutations .
we report the first two korean cases of pnd with mutations in the kcnj11 gene encoding kir6.2 .
in addition , we also show that oral sulfonylurea therapy is as good as or better for glycemic control , compared with insulin therapy .
two korean children with permanent neonatal diabetes were evaluated . neither the parents nor their siblings had diabetes .
case 1 , born at 40 weeks gestation , was well at birth but had intrauterine growth retardation with a birth weight of 2,300 g ( <3 percentile ) .
, diabetes was diagnosed based on hyperglycemia ( 1,460 mg / dl ) and glucosuria ( 3 + ) with ketoacidosis .
the serum c - peptide was 0.4 ng / ml ( normal range : 1.0 - 3.5 ) and hba1c was 6.9% ( normal range , 2.1 - 7.7 ) .
insulin therapy was initiated and insulin doses of 0.6 - 0.8 units / kg / day were required .
there was marked catch - up growth after birth , and the weight and height were normally distributed on follow - up after 6.5 yr .
we started with glibenclamide at a dose of 0.2 mg / kg / day , consisting of four doses a day and increased the doses up to 0.9 mg / kg / day over eight days .
this patient was born after 37 weeks gestation by cesarean section delivery with a birth weight of 3,000 g ( 10 - 25 percentile ) .
, diabetes was diagnosed based on hyperglycemia ( > 500 mg / dl ) and glucosuria ( 3 + ) with ketoacidosis .
autoantibodies associated with type 1 diabetes were not present , and the pancreatic ultrasonography was negative .
insulin therapy was initiated and the average daily insulin dose before sulfonylurea therapy was 0.6 units per kg .
the patient is now 3.8 yr of age , and his weight is 13.5 kg ( 3 - 10 percentile ) , and height is 100.0 cm ( 50 - 75 percentile ) , and the head circumference is 51.0 cm ( 50 - 75 percentile ) .
the serum c - peptide was 0.08 ng / ml , and hba1c was 8.7% .
at the age of 3.8 yr , he was admitted for a trial of glibenclamide therapy .
the insulin therapy was discontinued over two days , and glinbenclamide was given with an initial dose of 0.05 mg / kg four times a day , and the dose was increased up to 0.9 mg / kg / day .
genomic dna was isolated from peripheral blood using a puregene dna isolation kit ( gentra , minneapolis , mn , u.s.a . ) .
five exons of the kcnj11 gene and their intronic flanking sequences were amplified by polymerase chain reaction ( pcr ) with five sets of primers ( table 1 ) .
electrophoresis and analysis of the reaction mixtures were performed on the abi 3100 genetic analyzer ( applied biosystems , foster city , ca , u.s.a . ) .
continuous glucose monitoring was performed using on the continuous glucose monitoring system ( cgms , medtronic minimed , sylmar , ca , u.s.a . ) three times in case 1 : at the initiation of glibenclamide therapy , one week and one month later after glinbenclamide therapy .
cgms is a holterstyle sensor that monitors glucose values continuously in subcutaneous tissue fluid within a range of 40 - 400 mg / dl .
case 1 , born at 40 weeks gestation , was well at birth but had intrauterine growth retardation with a birth weight of 2,300 g ( <3 percentile ) .
, diabetes was diagnosed based on hyperglycemia ( 1,460 mg / dl ) and glucosuria ( 3 + ) with ketoacidosis .
the serum c - peptide was 0.4 ng / ml ( normal range : 1.0 - 3.5 ) and hba1c was 6.9% ( normal range , 2.1 - 7.7 ) .
insulin therapy was initiated and insulin doses of 0.6 - 0.8 units / kg / day were required .
there was marked catch - up growth after birth , and the weight and height were normally distributed on follow - up after 6.5 yr .
we started with glibenclamide at a dose of 0.2 mg / kg / day , consisting of four doses a day and increased the doses up to 0.9 mg / kg / day over eight days .
this patient was born after 37 weeks gestation by cesarean section delivery with a birth weight of 3,000 g ( 10 - 25 percentile ) .
, diabetes was diagnosed based on hyperglycemia ( > 500 mg / dl ) and glucosuria ( 3 + ) with ketoacidosis .
autoantibodies associated with type 1 diabetes were not present , and the pancreatic ultrasonography was negative .
insulin therapy was initiated and the average daily insulin dose before sulfonylurea therapy was 0.6 units per kg .
the patient is now 3.8 yr of age , and his weight is 13.5 kg ( 3 - 10 percentile ) , and height is 100.0 cm ( 50 - 75 percentile ) , and the head circumference is 51.0 cm ( 50 - 75 percentile ) .
the serum c - peptide was 0.08 ng / ml , and hba1c was 8.7% .
he did not have epilepsy , and the electroencephalogram was normal limits . at the age of 3.8 yr
the insulin therapy was discontinued over two days , and glinbenclamide was given with an initial dose of 0.05 mg / kg four times a day , and the dose was increased up to 0.9 mg / kg / day .
genomic dna was isolated from peripheral blood using a puregene dna isolation kit ( gentra , minneapolis , mn , u.s.a . ) .
five exons of the kcnj11 gene and their intronic flanking sequences were amplified by polymerase chain reaction ( pcr ) with five sets of primers ( table 1 ) .
electrophoresis and analysis of the reaction mixtures were performed on the abi 3100 genetic analyzer ( applied biosystems , foster city , ca , u.s.a . ) .
continuous glucose monitoring was performed using on the continuous glucose monitoring system ( cgms , medtronic minimed , sylmar , ca , u.s.a . ) three times in case 1 : at the initiation of glibenclamide therapy , one week and one month later after glinbenclamide therapy .
cgms is a holterstyle sensor that monitors glucose values continuously in subcutaneous tissue fluid within a range of 40 - 400 mg / dl .
we identified two previously reported heterozygous mutations ( a a - to - g change at nucleotide 509 , which resulted in a lysine - to - arginine substitution at position 170 of the gene encoding kir6.2 , k170r , in case 1 , and a g - to - a change at nucleotide 175 , which resulted in a valine - to - methionine substitution at position 59 in the gene encoding kir6.2 , v59 m , in case 2 , fig .
1 ) . in order to assess the pancreatic -cell function , c - peptide levels were measured in the patients with pnd . on admission for glibenclamide therapy ,
c - peptide levels were 0.1 in case 1 and 0.1 ng / ml in case 2 with corresponding blood glucose levels of 119 and 400 mg / dl , respectively .
the basal levels of c - peptide levels , after one week of glibenclamide treatment , were increased to more than 18 times higher than the levels obtained during insulin therapy in case 1 and case 2 ( table 2 ) . in order to compare the clinical response to glibenclamide treatment with the response to the insulin therapy , frequent capillary glucose measurement and cgms were performed .
after seven days of glibenclamide treatment , no hyper- or hypoglycemic episode was observed in these patients .
these patients remain well and off insulin at 6 and 15 months of follow - up .
recently , it has been shown that pnd can result from mutations in kir6.2 that reduce the ability for atp to close the atp - sensitive k+ channel .
we report here two different heterozygous activating mutations of the kcnj11 gene in korean children with pnd .
pnd is defined as hyperglycemia diagnosed within the first three months of life and requires insulin therapy for life ( 1 ) .
although pnd is a rare entity and the genetic etiology is unknown in about half of affected patients , kir6.2 mutations are a common cause of pnd . to date , at least 63 patients with activating mutations in kir6.2 have been described from europe , the middle east , australia , and north and south america , comprising 21 different mutations in 49 families ( 8 , 9 ) .
the majority of cases have been caucasian , but mutations have been found in other ethnic groups .
however , there has been only one report from japan in asia with pnd caused by a kir6.2 mutation ( 10 ) .
the cases reported here are the first cases of pnd with kir6.2 mutations identified in korea .
we found two different mutations ( v59 m and k170r ) in the korean patients with pnd .
the v59 m mutation is one of the most common mutations identified to date ( 8) .
however , the k170r mutation is rare , and only one case has been reported .
most patients with a mutation at r201 , the most common mutation , have nonremitting neonatal diabetes without neurological features .
however , patients with the v59 m mutation have developmental delay and features consistent with intermediate dend ( developmental delay , epilepsy , and neonatal diabetes ) syndrome ( 8) . the phenotypic expressions of the two patients presented here are similar to those reported in cases previously ( 8 , 9 ) .
our patients did not have type 1 associated antibodies and had low levels of c - peptide .
one of two patients had low birth weight . moreover , this patient was small for gestational age .
both exhibited severe hyperglycemia and the need for subsequent exogenous insulin within three months of life .
by contrast , patients with the v59 m mutation have neurological features ( developmental delay and muscles weakness ) in addition to diabetes . all mutations studied to date produce a marked decrease in the ability of atp to block the katp channels when expressed in the heterologous systems ( 11 - 13 ) . this reduction in atp sensitivity
causes the channel to open more fully at physiologically relevant concentrations of atp , leading to an increase in the katp current . in pancreatic -cells ,
an increase in katp current will hyperpolarize the membrane , suppressing electrical activity , ca influx , and insulin secretion , and thereby causes diabetes ( 14 ) .
katp channels that are insensitive to atp as a consequence of kir6.2 mutations can still be closed by sulfonylurea that bind to the sur subunit and directly close the channel ( 6 ) .
a number of patients with kir6.2 mutations have been able to discontinue their insulin injections completely and obtain as good as , or better glycemic control , using oral sulfonylurea ( 7 , 15 - 17 ) . in our cases , we discontinued insulin injection and introduced high dose oral glibenclamide therapy ( 0.8 - 0.9 mg / kg / day ) .
the continuous glucose monitoring systems were comparable during and after insulin treatment , and the hba1c levels declined after insulin had been discontinued . however , these patients still required high doses of sulfonylurea , compared with adults with type 2 diabetes , as has been reported in other studies ( 15 - 17 ) .
mutations that affect the probability of opening the channel are less sensitive to inhibition by sulfonylurea in vitro ( 13 , 18 ) .
therefore , even higher drug doses may be necessary in patients with pnd . to date ,
the longest duration recorded in a patient has remained off insulin has been about two years ( 8) .
therefore , long - term follow - up studies are now required to assess whether the response to sulfonylurea is maintained , and whether sulfonylurea therapy is better than insulin therapy . in conclusion ,
mutations in the gene kcnj11 encoding kir6.2 can cause pnd in korean children , and oral sulfonylurea therapy is as good as , or better than glycemic control , obtained with insulin therapy .
all patients with pnd should be tested for kcnj11 mutations for appropriate management and follow - up .
permanent neonatal diabetes ( pnd ) is a rare form of diabetes characterized by insulin - requiring hyperglycemia diagnosed within the first three months of life . in most cases , 
 the causes are not known . 
 recently , mutations in the kcnj11 gene encoding the kir6.2 subunit of the atp - sensitive k+ channel have been described in patients with pnd . 
 we report the first two korean cases with pnd due to a lysineto- arginine substitution at position 170 ( k179r ) and a valine - to - methionine substitution at position 59 ( v59 m ) mutations of kcnj11 encoding kir6.2 , respectively . 
 after several years of insulin therapy , these patients were managed by oral glibenclamide therapy at a daily dose of 0.8 - 0.9 mg / kg . 
 their basal c - peptide levels increased after one week of glibenclamide therapy , and one month later , the insulin and c - peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia . 
 these cases demonstrate that oral sulfonylurea may be the treatment of choice in pnd patients with kcnj11 mutations even at a young age .