a white , european , 33-year - old woman was diagnosed with gdm at 32 weeks gestation in her first pregnancy ( 75-g oral glucose tolerance test [ ogtt ] = 5.8 , 9.9 , and 8.0 mmol / l [ fasting , 1 h , and 2 h , respectively ] ) . she delivered a healthy girl , weighing 3,405 g ( 50th percentile ) , at 39 weeks gestation . a heterozygous gck mutation ( c.1340g > a , p.arg447gln ) was found in the mother on sequencing performed because of a three - generation paternal history of diabetes , persistent fasting hyperglycemia , and small glucose increment in a postpartum ogtt ( 7.0 , 7.5 , and 7.9 mmol / l ) ( 8) . during her second pregnancy , her initial self - monitored blood glucose levels were 6 mmol / l , fasting , and 68 mmol / l , 1-h postmeal . chorionic villus sampling ( cvs ) had been undertaken at 13 weeks gestation after high - risk first - trimester aneuploidy screening ( normal result ) . urgent sequencing of dna from this sample at 18 weeks gestation found the fetus to be heterozygous for the gck mutation . thus , insulin treatment was not initiated in the second or third trimester despite fasting and postprandial hyperglycemia on self - monitoring ( fig . she delivered a normal boy , weighing 3,415 g ( 51st percentile ) , at 39 weeks gestation . a : median and range of capillary glucose by time of day for patient 1 showing hyperglycemia above conventional treatment targets from 29 to 31 weeks gestation . b : median and range of capillary glucose by time of day for patient 2 showing hyperglycemia above conventional treatment targets from 29 to 31 weeks gestation . ( a high - quality color representation of this figure is available in the online issue . ) a white , european , 33-year - old woman was diagnosed with gdm at 32 weeks gestation in her first pregnancy ( 75-g oral glucose tolerance test [ ogtt ] = 5.8 , 9.9 , and 8.0 mmol / l [ fasting , 1 h , and 2 h , respectively ] ) . she delivered a healthy girl , weighing 3,405 g ( 50th percentile ) , at 39 weeks gestation . a heterozygous gck mutation ( c.1340g > a , p.arg447gln ) was found in the mother on sequencing performed because of a three - generation paternal history of diabetes , persistent fasting hyperglycemia , and small glucose increment in a postpartum ogtt ( 7.0 , 7.5 , and 7.9 mmol / l ) ( 8) . during her second pregnancy , her initial self - monitored blood glucose levels were 6 mmol / l , fasting , and 68 mmol / l , 1-h postmeal . chorionic villus sampling ( cvs ) had been undertaken at 13 weeks gestation after high - risk first - trimester aneuploidy screening ( normal result ) . urgent sequencing of dna from this sample at 18 weeks gestation found the fetus to be heterozygous for the gck mutation . thus , insulin treatment was not initiated in the second or third trimester despite fasting and postprandial hyperglycemia on self - monitoring ( fig . she delivered a normal boy , weighing 3,415 g ( 51st percentile ) , at 39 weeks gestation . a : median and range of capillary glucose by time of day for patient 1 showing hyperglycemia above conventional treatment targets from 29 to 31 weeks gestation . b : median and range of capillary glucose by time of day for patient 2 showing hyperglycemia above conventional treatment targets from 29 to 31 weeks gestation . ( a high - quality color representation of this figure is available in the online issue . ) in her first pregnancy , a white , european , 43-year - old woman had selective fetocide at 17 weeks gestation for dichorionic twins discordant for trisomy 21 . she delivered a healthy boy at 38 weeks , weighing 3,000 g ( 21st percentile ) . the pattern of glucose values ( ogtt at 28 weeks = 5.5 and 8.3 mmol / l [ fasting and 2 h ] ) ( 8) , paternal , diet - treated diabetes , and bmi = 22.7 kg / m suggested a diagnosis of gck hyperglycemia , which was confirmed on sequencing ( heterozygous gck mutation c.370g > a , p.asp124asn ) . self - monitored glucose levels were 5.26.7 mmol / l , fasting , and 5.810.2 mmol / l , 1-h postmeal ( fig . treatment with insulin was considered in line with conventional guidelines of the management of gdm ( 2 ) . cvs had been undertaken at 12 weeks gestation after high - risk first - trimester aneuploidy screening ( normal result ) . urgent sequencing of dna from this sample confirmed the fetus had inherited the gck mutation . the patient delivered a normal boy , weighing 3,590 g ( 55th percentile ) , at 38 weeks gestation . in her first pregnancy , a white , european , 43-year - old woman had selective fetocide at 17 weeks gestation for dichorionic twins discordant for trisomy 21 . she delivered a healthy boy at 38 weeks , weighing 3,000 g ( 21st percentile ) . the pattern of glucose values ( ogtt at 28 weeks = 5.5 and 8.3 mmol / l [ fasting and 2 h ] ) ( 8) , paternal , diet - treated diabetes , and bmi = 22.7 kg / m suggested a diagnosis of gck hyperglycemia , which was confirmed on sequencing ( heterozygous gck mutation c.370g > a , p.asp124asn ) . self - monitored glucose levels were 5.26.7 mmol / l , fasting , and 5.810.2 mmol / l , 1-h postmeal ( fig . treatment with insulin was considered in line with conventional guidelines of the management of gdm ( 2 ) . cvs had been undertaken at 12 weeks gestation after high - risk first - trimester aneuploidy screening ( normal result ) . urgent sequencing of dna from this sample confirmed the fetus had inherited the gck mutation . the patient delivered a normal boy , weighing 3,590 g ( 55th percentile ) , at 38 weeks gestation . in these two cases of gdm , due to a mutation in the gck gene , antenatal genetic testing showed the fetuses had inherited the gck mutation . as a result , neither mother received insulin treatment for established maternal hyperglycemia . the children had normal birth weights ( 51st and 55th percentiles ) and did not have any metabolic complications . normal birth weight is the usual outcome of gdm resulting from a gck mutation if the fetus inherits the mutation and maternal hyperglycemia is not treated ( 5 ) . heterozygous gck mutations cause a regulated rise in fasting plasma glucose , typically 5.58.0 mmol / l ( 1 ) . this raised glucose results in appropriate fetal insulin secretion because the affected fetus has the same homeostatic glucose set point as its mother ( 5 ) . insulin is not recommended for pregnancies in which the fetus has inherited the mutation because it can result in low birth weight ( 6 ) . in contrast , when the fetus is unaffected , macrosomia is common , and treatment with insulin to achieve maternal euglycemia is appropriate . the clinical dilemma of managing pregnant women with gck mutations is due to uncertainty about the fetal genotype . although unreliable ( 9 ) , current advice is to measure fetal growth using serial ultrasound scans as a surrogate for fetal genotype , to guide diabetes and obstetric management . in pregnancies with accelerating fetal growth ( abdominal circumference > 75th percentile ) intensive insulin treatment should be initiated , aimed at lowering elevated blood glucose levels to normal pregnancy ranges . large insulin doses of > 1 u / kg / day ( 6 ) may be required to overcome maternal glucose homeostasis , which can be difficult to achieve without causing symptoms of hypoglycemia . in these two cases , knowledge that the fetuses had inherited the gck mutation allowed the maternal hyperglycemia in pregnancy to remain untreated . we recommend that if a pregnant woman with a gck mutation has a cvs or amniocentesis for another reason , the fetal dna should be tested for the gck mutation . however , the 1% miscarriage rates associated with these procedures ( 10 ) means they are not routinely warranted for fetal genetic diagnosis in this situation . in the future , noninvasive prenatal diagnosis using cell - free fetal dna or fetal cells in maternal blood ( 11 ) has the potential to determine fetal genotype and therefore influence the management of gck - mody ( maturity - onset diabetes of the young ) in pregnancy without the attendant risks associated with invasive prenatal testing .
objectivein women with hyperglycemia due to heterozygous glucokinase ( gck ) mutations , the fetal genotype determines its growth . if the fetus inherits the mutation , birth weight is normal when maternal hyperglycemia is not treated , whereas intensive treatment may adversely reduce fetal growth . 
 however , fetal genotype is not usually known antenatally , making treatment decisions difficult.history and examinationwe report two women with gestational diabetes mellitus resulting from gck mutations with hyperglycemia sufficient to merit treatment.investigationin both women , dna from chorionic villus sampling , performed after high - risk aneuploidy screening , showed the fetus had inherited the gck mutation . 
 therefore , maternal hyperglycemia was not treated . 
 both offspring had a normal birth weight and no peripartum complications.conclusionsin pregnancies where the mother has hyperglycemia due to a gck mutation , knowing the fetal gck genotype guides the management of maternal hyperglycemia . 
 fetal genotyping should be performed when fetal dna is available from invasive prenatal diagnostic testing .