Clinical Heterogeneity in Monogenic Diabetes Caused by Mutations in the Glucokinase Gene (GCK-MODY)

• Published in: Diabetes care Vol. 33; no. 2; pp. 290 - 292
• Main Authors: Cuesta-Muñoz, Antonio L, Tuomi, Tiinamaija, Cobo-Vuilleumier, Nadia, Koskela, Hanna, Odili, Stella, Stride, Amanda, Buettger, Carol, Otonkoski, Timo, Froguel, Philippe, Grimsby, Joseph, Garcia-Gimeno, Maria, Matschinsky, Franz M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2010
• Subjects: Adult; Biological and medical sciences; Blood Glucose; Blood Glucose - metabolism; Codon; Codon - genetics; codons; Dextrose; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Family; Female; Genetic aspects; Genetic counseling; genetics; glucokinase; Glucokinase - genetics; Glucose; glucose tolerance; Glucose Tolerance Test; Glucose tolerance tests; homeostasis; Humans; Hyperglycemia; insulin; insulin resistance; Isoenzymes; Male; Medical sciences; Metabolic diseases; Metabolic disorders; metabolism; Miscellaneous; Mutation; noninsulin-dependent diabetes mellitus; Original Research; Pregnancy; Public health. Hygiene; Public health. Hygiene-occupational medicine; Studies; Young Adult; Endocrinopathy; Human; Maturity onset diabetes young; Nutrition; Enzyme; Transferases; Metabolic diseases; Monogenic; Genetic disease; Heterogeneity; Gene; Glucokinase; Genetics; Mutation; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc09-0681

OBJECTIVE: To evaluate the heterogeneity in the clinical expression in a family with glucokinase mature-onset diabetes of the young (GCK-MODY). RESEARCH DESIGN AND METHODS: Members (three generations) of the same family presented either with overt neonatal hyperglycemia, marked postprandial hyperglycemia, or glucosuria. Homeostasis model assessment of insulin resistance (HOMAIR) and insulinogenic and disposition indexes were calculated. Oral glucose tolerance test (OGTT) results in the GCK mutation carriers from this family were compared with those from other subjects with GCK mutations in the same codon (GCK₂₆₁), with other missense and other types of GCK mutations in different codons from the European MODY Consortium database (GCKm). RESULTS: Mutation G261R was found in the GCK gene. During the OGTT, glucose (P = 0.02) and insulin (P = 0.009) response at 2 h as well as at the 2-h glucose increment (GCK₂₆₁ versus other missense GCK mutations, P = 0.003) were significantly higher in GCK₂₆₁ than in GCKm carriers. CONCLUSIONS: Differing from other GCKm carriers, the glucose and insulin response to oral glucose was significantly higher in GCK₂₆₁ carriers, indicating clinical heterogeneity in GCK-MODY.