Glucokinase mutations in young children with hyperglycemia

Abstract

We conclude that molecular evaluation for MODY in children with mild fasting hyperglycemia without ketosis with family histories of diabetes can provide important prognostic information to guide therapy and exclude preclinical type 1 diabetes mellitus.

Mild fasting hyperglycemia in children: high rate of glucokinase mutations and some risk of developing type 1 diabetes mellitus

“…Upon identification of an Arg191Gln GCK mutation, insulin treatment was discontinued and the HbA1c levels remained stable. The second family in which insulin treatment was discontinued has been reported previously (8) (Fig. 1B).…”

“…Genomic DNA was isolated from leukocytes in whole blood by cell lysis followed by DNA extraction and precipitation according to manufacturer’s instructions (Promega, Madison, WI, USA). Each proband was amplified by polymerase chain reaction (PCR) and purified as previously described (8) Amplicons were bidirectionally sequenced for all the coding exons and splice sites of GCK and HNF1A with the BigDye Terminator kit using an ABI 377 sequencer (Applied Biosystems, Foster City, CA, USA). When a mutation was identified, all other family members were sequenced only for the exon containing the mutation.…”

Diagnostic screening of MODY2/GCKmutations in the Norwegian MODY Registry

“…However, transition to diet did not deteriorate their metabolic control (personal communication from the patients). Similar cases have also been reported elsewhere (37, 38).…”

Hyperinsulinism and Diabetes: Genetic Dissection of β Cell Metabolism-Excitation Coupling in Mice

“…Heterozygous β-cell GCK +/− mutant mice show glucose-intolerance and impaired GSIS (Bali et al, 1995; Grupe et al, 1995; Sakura et al, 1998) but again, the diabetes does not progress, reiterating the MODY-2 phenotype. Why the phenotype is non-progressive, in humans and mice, is interesting, since the level of hyperglycemia that is reached (typically fasted blood glucose of ~ 125-135 mg/dL (Codner et al, 2006; Fajans et al, 2001; Shehadeh et al, 2005) is one that progresses to uncontrollable levels in other forms of diabetes, including human type-2 (Guillausseau et al, 2008; Matveyenko and Butler, 2008). Insulin levels are typically normal, such that decreased insulin/glucose ratio suggests increased insulin sensitivity, in humans and mice (Grupe et al, 1995; Katagiri et al, 1992; Terauchi et al, 1995).…”