GCK-MODY in the US National Monogenic Diabetes Registry: frequently misdiagnosed and unnecessarily treated.
OBJECTIVE
GCK-MODY leads to mildly elevated blood glucose typically not requiring therapy. It has been described in all ethnicities, but mainly in Caucasian Europeans. Here we describe our US cohort of GCK-MODY.


METHODS
We examined the rates of detection of heterozygous mutations in the GCK gene in individuals referred to the US Monogenic Diabetes Registry with a phenotype consistent with GCK-MODY. We also assessed referral patterns, treatment and demography, including ethnicity, of the cohort.


RESULTS
Deleterious heterozygous GCK mutations were found in 54.7 % of Registry probands selected for GCK sequencing for this study. Forty-nine percent were previously unnecessarily treated with glucose-lowering agents, causing hypoglycemia and other adverse effects in some of the subjects. The proportion of probands found to have a GCK mutation through research-based testing was similar across each ethnic group. However, together African-American, Latino and Asian subjects represented only 20.5 % of screened probands and 17.2 % of those with GCK-MODY, despite higher overall diabetes prevalence in these groups.


CONCLUSIONS
Our data show that a high detection rate of GCK-MODY is possible based on clinical phenotype and that prior to genetic diagnosis, a large percentage are inappropriately treated with glucose-lowering therapies. We also find low minority representation in our Registry, which may be due to disparities in diagnostic diabetes genetic testing and is an area needing further investigation.
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, USA.
David
D
Carmody
Departments of Pediatrics and Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, 60637, USA. rnaylor@peds.bsd.uchicago.edu.
Rochelle N
RN
Naylor
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, USA.
Charles D
CD
Bell
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, USA.
Shivani
S
Berry
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, USA.
Jazzmyne T
JT
Montgomery
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, USA.
Elizabeth C
EC
Tadie
Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, USA.
Jessica L
JL
Hwang
Departments of Pediatrics and Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, 60637, USA.
Siri Atma W
SA
Greeley
Departments of Pediatrics and Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, The University of Chicago, Chicago, IL, 60637, USA.
Louis H
LH
Philipson
D000293:Adolescent; D000328:Adult; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000628:therapy; D003937:Diagnosis, Differential; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012042:Registries / Q000592:standards*; D015983:Selection Bias; D014481:United States
D005941:Glucokinase
GCK; Genetic testing; Glucokinase; MODY; Monogenic diabetes