A novel genetic mutation in a Portuguese family with GCK-MODY

Almeida, Claudia Rejane Chiarel; Silva, Sónia Regina; Garcia, E.; Leite, Ana Luísa; Teles, Andreia; Campos, Rosa María Píriz

doi:10.1515/jpem-2013-0056

Cited by 3 publications

(2 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We originally posed the question of what is the impact of pharmacological and non-pharmacological glucose lowering therapy in GCK-related hyperglycemia. However, we identified only one case report that presented data on active pharmacological intervention 12 and one study on dietary intervention 13 and the rest of the 10 studies [14][15][16][17][18][19][20][21][22][23] assessed the impact of stopping anti-hyperglycemic agents on HbA1c or glucose or assessed the stability of HbA1c over time on no therapy (Table 3). Thus, we concentrated on analyzing the evidence to support or refute non-treatment of GCK-related hyperglycemia.…”

Section: A) Gck-related Hyperglycemiamentioning

confidence: 99%

“…Most studies on GCK-related hyperglycemia looked at within individual stability of HbA1c over time without glucose lowering therapy (175 individuals from case reports and cohort data, range of time between 3-126 months) 14,16,18,[20][21]23 or after cessation of pharmacologic therapy following genetic diagnosis (35 individuals from case reports and cohort data) 15,[19][20][22][23] . All studies showed stability of HbA1c with no significant change including when glucose lowering therapy of either oral hypoglycemic agents (OHA) or insulin was discontinued (table 3).…”

Section: A) Gck-related Hyperglycemiamentioning

confidence: 99%

See 1 more Smart Citation

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Naylor

Patel

Kettunen

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for a precision medicine approach. We systematically reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-diabetes, HNF4A-diabetes, HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes (Thiamine-Responsive Megaloblastic Anemia, TRMA). Methods: Systematic review with data sources from PubMed, MEDLINE and Embase were performed answering specific therapeutic questions for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes. Results: 147 studies met inclusion criteria with only six experimental studies (four randomized trials for HNF1A-diabetes) and the rest being single case reports or cohort studies. Most studies were rated as having moderate or serious risk of bias. For GCK-related hyperglycemia, six studies (35 individuals) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited to three studies (16 individuals) showing lower HbA1c with SU therapy. The 13 studies in HNF1B-diabetes (n=301) and 10 in MD with m.3243A>G variant (n=250) showed that while some patients can be treated with oral agents the majority of patients were insulin treated. In HNF1B-diabetes the attempts to transfer from insulin to oral hypoglycemic agents (OHA) were unsuccessful in most cases. In 6q24-TND there were insufficient studies supporting OHA close to diagnosis before remission but more support for their use after relapse. In SLC19A2-diabetes there was some evidence that treatment with thiamine improved glycemic control and reduced insulin requirement while less than half achieved insulin-independency. Conclusion: There is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The combined data does support: no treatment being needed in GCK-related hyperglycemia; SU being used as the first line treatment in HNF1A-diabetes; SU can be tried in HNF4A-diabetes; insulin often needed in HNF1B-diabetes and MD with the m.3243A>G variant; SU can be tried in 6q24-TND relapse; and thiamine may improve glycemic control in SLC19A2-diabetes. Further evidence, particularly randomized comparative studies, are needed to examine the optimum treatment for glycemic response in all monogenic subtypes.

show abstract

Section: A) Gck-related Hyperglycemiamentioning

confidence: 99%

Section: A) Gck-related Hyperglycemiamentioning

confidence: 99%

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Naylor

Patel

Kettunen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Precision treatment of beta-cell monogenic diabetes: a systematic review

Naylor,

Patel,

Kettunen

et al. 2024

Commun Med

View full text Add to dashboard Cite

Background Beta-cell monogenic forms of diabetes have strong support for precision medicine. We systematically analyzed evidence for precision treatments for GCK-related hyperglycemia, HNF1A-, HNF4A- and HNF1B-diabetes, and mitochondrial diabetes (MD) due to m.3243 A > G variant, 6q24-transient neonatal diabetes mellitus (TND) and SLC19A2-diabetes. Methods The search of PubMed, MEDLINE, and Embase for individual and group level data for glycemic outcomes using inclusion (English, original articles written after 1992) and exclusion (VUS, multiple diabetes types, absent/aggregated treatment effect measures) criteria. The risk of bias was assessed using NHLBI study-quality assessment tools. Data extracted from Covidence were summarized and presented as descriptive statistics in tables and text. Results There are 146 studies included, with only six being experimental studies. For GCK-related hyperglycemia, the six studies (35 individuals) assessing therapy discontinuation show no HbA1c deterioration. A randomized trial (18 individuals per group) shows that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes. Cohort and case studies support SU’s effectiveness in lowering HbA1c. Two cross-over trials (each with 15–16 individuals) suggest glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes is limited. Most reported patients with HNF1B-diabetes (N = 293) and MD (N = 233) are on insulin without treatment studies. Limited data support oral agents after relapse in 6q24-TND and for thiamine improving glycemic control and reducing/eliminating insulin requirement in SLC19A2-diabetes. Conclusion There is limited evidence, and with moderate or serious risk of bias, to guide monogenic diabetes treatment. Further evidence is needed to examine the optimum treatment in monogenic subtypes.

show abstract

Identification of Variants Responsible for Monogenic Forms of Diabetes in Brazil

et al. 2022

View full text Add to dashboard Cite

Monogenic forms of diabetes mellitus may affect a significant number of patients of this disease, and it is an important molecular cause to be investigated. However, studies of the genetic causes of monogenic diabetes, especially in populations with mixed ethnic backgrounds, such as the one in Brazil, are scarce. The aim of this study was to screen several genes associated with monogenic diabetes in fifty-seven Brazilian patients with recurrence of the disease in their families and thirty-four relatives. Inclusion criteria were: Age of onset ≤ 40 years old, BMI < 30 kg/m², at least two affected generations and negative anti-GAD and anti-IA2 antibodies. MODY genes HNF4A, GCK, HNF1A, HNF1B, NEUROD1, KLF11, PAX4, INS, KCNJ11, and MT-TL1 were sequenced by Sanger sequencing. We identified a total of 20 patients with variants, 13 GCK-MODY, four HNF1A-MODY, and one variant in each of the following genes, HNF4A, HNF1B and MT-TL1. Segregation analysis was performed in 13 families. Four variants were novel, two in GCK (p.(Met115Val) [c.343A>G] and p.(Asp365GlufsTer95) [c.1094_1095insGCGA]) and two in HNF1A (p.(Tyr163Ter) [c.489C>G] and p.(Val380CysfsTer39) [c.1136_1137insC]). Here we highlight the importance of screening for monogenic diabetes in admixed populations.

show abstract

A novel genetic mutation in a Portuguese family with GCK-MODY

Cited by 3 publications

References 5 publications

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Precision treatment of beta-cell monogenic diabetes: a systematic review

Identification of Variants Responsible for Monogenic Forms of Diabetes in Brazil

Contact Info

Product

Resources

About