Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing?

Delvecchio, Maurizio; Salzano, Giuseppina; Bonura, Clara; Cauvin, Vittoria; Cherubini, Valentino; d’Annunzio, Giuseppe; Franzese, Adriana; Giglio, Sabrina; Grasso, V.; Graziani, Vanna; Iafusco, Dario; Lera, Rosa Fernández; Maffeis, Claudio; Maltoni, Giulio; Mantovani, Vilma; Menzaghi, Claudia; Patera, Patrizia Ippolita; Rabbone, Ivana; Reindstadler, Petra; Scelfo, Sabrina; Tinto, Nadia; Toni, Sonia; Tumini, Stefano; Lombardo, Fortunato; Nicolucci, Antonio; Barbetti, Fabrizio

doi:10.1007/s00592-018-1179-y

Cited by 14 publications

(13 citation statements)

References 5 publications

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“…Indication for genetic testing for MODY is based on clinical criteria [ 14 ]. Simple and inexpensive criteria to distinguish GCK from HNF1A MODY using glycemic control parameters have been suggested [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

A decision algorithm to identify patients with high probability of monogenic diabetes due to HNF1A mutations

et al. 2019

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Purpose To investigate the utility of biomarkers of maturity-onset diabetes of the young (MODY), high-sensitivity C-reactive protein (hsCRP), and 1,5-anhydroglucitol (1,5-AG) in conjunction with other clinical and laboratory features to improve diagnostic accuracy and provide a diagnostic algorithm for HNF1A MODY. Methods We examined 77 patients with HNF1A MODY, 88 with GCK MODY mutations, 99 with type 1 diabetes, and 92 with type 2 diabetes. In addition to 1,5-AG and hsCRP, we considered body mass index (BMI), fasting glucose, and fasting serum C-peptide as potential biomarkers. Logistic regression and receiver operating characteristic curves were used in marker evaluation. Results Concentration of hsCRP was lowest in HNF1A MODY (0.51 mg/l) and highest in type 2 diabetes (1.33 mg/l). The level of 1,5-AG was lowest in type 1 diabetes and HNF1A MODY, 3.8 and 4.7 μg/ml, respectively, and highest (11.2 μg/ml) in GCK MODY. In the diagnostic algorithm, we first excluded patients with type 1 diabetes based on low C-peptide (C-statistic 0.98) before using high BMI and C-peptide to identify type 2 diabetes patients (C-statistic 0.92). Finally, 1,5-AG and hsCRP in conjunction yielded a C-statistic of 0.86 in discriminating HNF1A from GCK MODY. We correctly classified 92.9% of patients with type 1 diabetes, 84.8% with type 2 diabetes, 64.9% HNF1A MODY, and 52.3% GCK MODY patients. Conclusions Plasma 1,5-AG and serum hsCRP do not discriminate sufficiently HNF1A MODY from common diabetes types, but could be potentially useful in prioritizing Sanger sequencing of HNF1A gene.

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Section: Introductionmentioning

confidence: 99%

A decision algorithm to identify patients with high probability of monogenic diabetes due to HNF1A mutations

et al. 2019

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“…Recognition of these forms of diabetes is crucial for reducing both the complications and the treatment costs associated with the disease, and to improve glycemic control with the most appropriate treatment and follow-up for patients [ 17 , 24 ]. In particular, HNF1A/MODY patients are generally responsive to sulfonylureas, whereas, for GCK/MODY patients, no pharmacological treatment is recommended and diet and regular physical activity are sufficient to maintain good glycemic control [ 6 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recognition of GCK/ and HNF1A/MODY, particularly when the patient is of pediatric age, is of fundamental importance, because this allows us to select the appropriate clinical management and to conserve healthcare resources. In fact, diabetic patients with HNF1A/MODY can avoid insulin and be treated with oral hypoglycemic agents such as sulfonylureas, to which they are particularly sensitive, whereas GCK/MODY patients, due to their mild phenotype, require less frequent clinical monitoring than patients with other forms of diabetes [ 14 , 15 ]. Therefore, molecular diagnosis of MODY may provide a perceptible impact on both the patient’s quality of life and the healthcare costs [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

et al. 2021

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Monogenic diabetes (MD) represents a heterogeneous group of disorders whose most frequent form is maturity-onset diabetes of the young (MODY). MD is predominantly caused by a mutation in a single gene. We report a case of a female patient with suspected MD and a positive family history for diabetes and obesity. In this patient, two gene variants have been identified by next-generation sequencing (NGS): one in the Glucokinase (GCK) gene reported in the Human Gene Mutation Database (HGMD) and in the literature associated with GCK/MODY, and the other in the hepatocyte nuclear factor 1A (HNF1A) gene not previously described. The GCK variant was also identified in the hyperglycemic father, whereas the HNF1A variant was present in the mother. This new case of digenic GCK/HNF1A variants identified in a hyperglycemic subject, evidences the importance of NGS analysis in patients with suspected MD. In fact, this methodology will allow us to both increase the number of diagnoses and to identify mutations in more than one gene, with a better understanding of the genetic cause, and the clinical course, of the disease.

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“…In persons with GCK-MODY, the regulation of insulin secretion occurs at a higher set point than in the normal population, resulting in impaired fasting glucose and impaired glucose tolerance. HbA1c is usually below 7.3-7.5% [19,20]. Patients are almost asymptomatic as blood glucose is below the level that causes osmotic symptoms.…”

Section: Clinical Presentationmentioning

confidence: 99%

Treatment Options for MODY Patients: A Systematic Review of Literature

2020

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Maturity-onset diabetes of the young (MODY) is an unusual form of diabetes with specific features that distinguish it from type 1 and type 2 diabetes. There are 14 known subtypes of MODY, and mutations in three genes (HNF1A, HNF4A, GCK) account for about 95% of all MODY cases. Diagnosis usually occurs before the age of 25 years, although less frequent forms may occur more often-but not necessarilylater in life. The molecular diagnosis may tailor the choice of the most appropriate treatment, with the aim to optimize blood glucose control, reduce the risk of hypoglycemic events and long-term complications, and enable proper genetic counseling. Treatment is usually unnecessary for patients with mutations in the GCK gene, while oral hypoglycemic agents (generally sulphonylureas) are recommended for patients with mutations in the HNF4A and HNF1A genes. More recent data show that other glucose-lowering agents can be effective in the latter patients, and additional and alternative therapies have been proposed. Proper management guidelines during pregnancy have been developed for carriers of GCK gene mutations, but such guidelines are still a subject of debate in other cases, although some recommendations are available. The other subtypes of MODY are even more rare, and very little data are available in the literature. In this review we summarize the most pertinent findings and recommendations on the treatment of patients with the different subtypes of MODY. Our aim is to provide the reader with an easy-to-read update that can be used to drive the clinician's therapeutical approach to these patients after the molecular diagnosis.

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Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing?

Cited by 14 publications

References 5 publications

A decision algorithm to identify patients with high probability of monogenic diabetes due to HNF1A mutations

A decision algorithm to identify patients with high probability of monogenic diabetes due to HNF1A mutations

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

Treatment Options for MODY Patients: A Systematic Review of Literature

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