Are Glucokinase Mutations Associated with Low Triglycerides?

Berger, Mario; Mönks, Detlev; Schmidt, Henriette; Krane, Vera; Wanner, Christoph; Walter, Ulrich; Lindner, Tom H.

doi:10.1373/clinchem.2004.045963

Cited by 9 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding was consistent with Berger et al. 16 who showed lower TG levels in affected GCK ‐MODY family members than in unaffected ones. Furthermore, an association between mildly increased GCK activity owing to rs780094 carriage and elevated HDL cholesterol levels has been demonstrated 14 .…”

Section: Discussionsupporting

confidence: 93%

“…Experimental models of constitutively overexpressed GCK in the liver resulted in elevated TG levels with no change of circulating total cholesterol. 15 This finding was consistent with Berger et al 16 who showed lower TG levels in affected GCK-MODY family members than in unaffected ones. Furthermore, an association between mildly increased GCK activity owing to rs780094 carriage and elevated HDL cholesterol levels has been demonstrated.…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults

Fendler

Borowiec

Antosik

et al. 2011

Clinical Endocrinology

View full text Add to dashboard Cite

Summary Introduction Confirmation of monogenic diabetes caused by glucokinase mutations (GCK‐MODY) allows pharmacogenetic intervention in the form of insulin discontinuation. This is especially important among paediatric and young adult populations where GCK‐MODY is most prevalent. Methods The study evaluated the utility of lipid parameters in screening for patients with GCK‐MODY. Eighty‐nine children with type 1 diabetes and 68 with GCK‐MODY were screened for triglyceride (TG), total and HDL cholesterol levels. Standardization against a control group of 171 healthy children was applied to eliminate the effect of development. Clinical applicability and cut‐off value were evaluated in all available patients with GCK‐MODY (n = 148), hepatocyte nuclear factor 1‐alpha‐MODY (HNF1A MODY) (n = 37) or type 1 diabetes (n = 221). Results Lower lipid parameter values were observed in GCK‐MODY than in patients with type 1 diabetes. Standard deviation scores were −0·22 ± 2·24 vs 1·31 ± 2·17 for HDL cholesterol (P < 0·001), −0·16 ± 2·14 vs 0·60 ± 1·77 for total cholesterol (P = 0·03) and −0·57 ± 0·97 vs−0·22 ± 0·97 for TG (P = 0·05). Validation analysis confirmed that HDL cholesterol was the best parameter for GCK‐MODY selection [sensitivity 87%, specificity 54%, negative predictive value (NPV) 86%, positive PV 56%]. A threshold HDL concentration of 1·56 mm offered significantly better diagnostic efficiency than total cholesterol (cut‐off value 4·51 mm; NPV 80%; PPV 38%; P < 0·001). TG did not offer a meaningful cut‐off value. Conclusions HDL cholesterol levels measured in individuals with likely monogenic diabetes may be useful in screening for GCK‐MODY and differentiation from T1DM and HNF1A‐MODY, regardless of treatment or metabolic control.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 88%

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults

Fendler

Borowiec

Antosik

et al. 2011

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

“…This finding supports the notion that mutations may affect GCK function, which is intimately related to intermotion domain [7]. Our data confirm the association between low triglyceride values and GCK mutations and support a low rate of cardiovascular complications in GCK MODY diabetes [36]. Interestingly, the two patients (M001 and M013) with the lowest BMI z scores also had the lowest FPIR values, which is in line with the finding that, at low levels, insulin does not exert an anabolic effect [37].…”

Section: Discussionsupporting

confidence: 90%

Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy

et al. 2008

View full text Add to dashboard Cite

BackgroundMaturity onset diabetes of the young type 2 (or GCK MODY) is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK).Methodology/Principal FindingsWe screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%); 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu) and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: ∼59%) than in the large (4/12: 33%) domain or in the connection (1/12: 8%) region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD) OGTT = 7.8 mMol/L (1.8)] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04).ConclusionsThe prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings) but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation.

show abstract

“…In contrast to some (although not all) studies that have reported lower TG levels in patients with GCK-DM compared with healthy controls, [24][25][26] only one study with a small size sample reported differences in TG between patients with GCK-DM and T2DM. 27 We observed that patients with GCK-DM had relatively lower TG levels than did patients with T2DM; this finding can be explained by the fact that patients with T2DM often have hypertriglyceridemia, and a small sample size is sufficient to identify this difference between GCK-DM and T2DM.…”

Section: Discussioncontrasting

confidence: 64%

A new clinical screening strategy and prevalence estimation for glucokinase variant-induced diabetes in an adult Chinese population

Han

Zhou

et al. 2019

Genetics in Medicine

View full text Add to dashboard Cite

Are Glucokinase Mutations Associated with Low Triglycerides?

Cited by 9 publications

References 10 publications

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults

Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy

A new clinical screening strategy and prevalence estimation for glucokinase variant-induced diabetes in an adult Chinese population

Contact Info

Product

Resources

About