Novel Use of GLP-1 Receptor Agonist Therapy in HNF4A-MODY

Broome, David T.; Tekin, Zehra; Pantalone, Kevin M.; Mehta, Adi

doi:10.2337/dc20-0012

Cited by 18 publications

(13 citation statements)

References 5 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though HNF1A- and HNF4A-MODY patients are responsive to sulfonylurea, this therapy has a significant risk of hypoglycaemia. Therefore, a combination with other glucose-lowering agents such as dipeptidyl peptidase-4 inhibitor [ 141 , 142 ] or monotherapy with glucagon-like peptide (GLP-1) receptor agonists were also tested [ 143 , 144 ]. Recently, the usage of incretin hormone glucose-dependent insulinotropic peptide (GIP) and GLP-1 were tested in patients with HNF1A-MODY.…”

Section: Diagnosis and Current Treatment Optionsmentioning

confidence: 99%

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Skoczek

Dulak

Kachamakova‐Trojanowska

2021

IJMS

View full text Add to dashboard Cite

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous group of monogenic endocrine disorders that is characterised by autosomal dominant inheritance and pancreatic β-cell dysfunction. These patients are commonly misdiagnosed with type 1 or type 2 diabetes, as the clinical symptoms largely overlap. Even though several biomarkers have been tested none of which could be used as single clinical discriminator. The correct diagnosis for individuals with MODY is of utmost importance, as the applied treatment depends on the gene mutation or is subtype-specific. Moreover, in patients with HNF1A-MODY, additional clinical monitoring can be included due to the high incidence of vascular complications observed in these patients. Finally, stratification of MODY patients will enable better and newer treatment options for MODY patients, once the disease pathology for each patient group is better understood. In the current review the clinical characteristics and the known disease-related abnormalities of the most common MODY subtypes are discussed, together with the up-to-date applied diagnostic criteria and treatment options. Additionally, the usage of pluripotent stem cells together with CRISPR/Cas9 gene editing for disease modelling with the possibility to reveal new pathophysiological mechanisms in MODY is discussed.

show abstract

Section: Diagnosis and Current Treatment Optionsmentioning

confidence: 99%

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Skoczek

Dulak

Kachamakova‐Trojanowska

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Low carbohydrate diet or low-dose sulfonylureas are used to manage HNF4A-MODY initially but insulin therapy is usually required in advanced disease or during pregnancy [ 21 , 69 , 70 ]. The beneficial role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the management of patients with HNF4A-MODY has recently been reported [ 75 ]. Even though this finding is clinically significant, prospective studies are needed to help establish which patients should be offered incretin-based therapy.…”

Section: Introductionmentioning

confidence: 99%

The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

Nkonge

2020

Clin Diabetes Endocrinol

View full text Add to dashboard Cite

Background The most common type of monogenic diabetes is maturity-onset diabetes of the young (MODY), a clinically and genetically heterogeneous group of endocrine disorders that affect 1–5% of all patients with diabetes mellitus. MODY is characterized by autosomal dominant inheritance but de novo mutations have been reported. Clinical features of MODY include young-onset hyperglycemia, evidence of residual pancreatic function, and lack of beta cell autoimmunity or insulin resistance. Glucose-lowering medications are the main treatment options for MODY. The growing recognition of the clinical and public health significance of MODY by clinicians, researchers, and governments may lead to improved screening and diagnostic practices. Consequently, this review article aims to discuss the epidemiology, pathogenesis, diagnosis, and treatment of MODY based on relevant literature published from 1975 to 2020. Main body The estimated prevalence of MODY from European cohorts is 1 per 10,000 in adults and 1 per 23,000 in children. Since little is known about the prevalence of MODY in African, Asian, South American, and Middle Eastern populations, further research in non-European cohorts is needed to help elucidate MODY’s exact prevalence. Currently, 14 distinct subtypes of MODY can be diagnosed through clinical assessment and genetic analysis. Various genetic mutations and disease mechanisms contribute to the pathogenesis of MODY. Management of MODY is subtype-specific and includes diet, oral antidiabetic drugs, or insulin. Conclusions Incidence and prevalence estimates for MODY are derived from epidemiologic studies of young people with diabetes who live in Europe, Australia, and North America. Mechanisms involved in the pathogenesis of MODY include defective transcriptional regulation, abnormal metabolic enzymes, protein misfolding, dysfunctional ion channels, or impaired signal transduction. Clinicians should understand the epidemiology and pathogenesis of MODY because such knowledge is crucial for accurate diagnosis, individualized patient management, and screening of family members.

show abstract

“…GLP-1 Receptor Activation (GLP1-RA) stimulates insulin secretion bypassing the genetic HNF1A defect through the elevation of cyclic adenosine monophosphate (cAMP) and activation of protein kinase A [ 122 , 123 , 124 ]. GLP1-RA has been, therefore, recently suggested as an add-on treatment in patients who do not achieve optimal glycemic control with sulfonylurea or who experience frequent hypoglycemic events [ 125 , 126 , 127 , 128 ].…”

Section: Hepatocyte Nuclear Factors (Hnf) Familymentioning

confidence: 99%

“…An alternative treatment for HNF4A-MODY patients are GLP-1 agonists that should be taken into consideration in case of either non-optimal glycemic control or recurrent hypoglycemia due to sulfonylureas [ 122 , 126 ].…”

Section: Hepatocyte Nuclear Factors (Hnf) Familymentioning

confidence: 99%

Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes

Marucci

Rutigliano

Fini

et al. 2022

Genes

View full text Add to dashboard Cite

Monogenic diabetes is a genetic disorder caused by one or more variations in a single gene. It encompasses a broad spectrum of heterogeneous conditions, including neonatal diabetes, maturity onset diabetes of the young (MODY) and syndromic diabetes, affecting 1–5% of patients with diabetes. Some of these variants are harbored by genes whose altered function can be tackled by specific actions (“actionable genes”). In suspected patients, molecular diagnosis allows the implementation of effective approaches of precision medicine so as to allow individual interventions aimed to prevent, mitigate or delay clinical outcomes. This review will almost exclusively concentrate on the clinical strategy that can be specifically pursued in carriers of mutations in “actionable genes”, including ABCC8, KCNJ11, GCK, HNF1A, HNF4A, HNF1B, PPARG, GATA4 and GATA6. For each of them we will provide a short background on what is known about gene function and dysfunction. Then, we will discuss how the identification of their mutations in individuals with this form of diabetes, can be used in daily clinical practice to implement specific monitoring and treatments. We hope this article will help clinical diabetologists carefully consider who of their patients deserves timely genetic testing for monogenic diabetes.

show abstract

Novel Use of GLP-1 Receptor Agonist Therapy in HNF4A-MODY

Cited by 18 publications

References 5 publications

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes

Contact Info

Product

Resources

About