Optimizing maturity-onset diabetes of the young detection in a pediatric diabetes population.
children
diabetes
maturity onset diabetes of the young
pediatric diabetes
Journal
Pediatric diabetes
ISSN: 1399-5448
Titre abrégé: Pediatr Diabetes
Pays: Denmark
ID NLM: 100939345
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
18
01
2022
received:
11
10
2021
accepted:
20
02
2022
pubmed:
27
2
2022
medline:
27
5
2022
entrez:
26
2
2022
Statut:
ppublish
Résumé
Maturity-onset diabetes of the young (MODY) is often misdiagnosed as type 1/type 2 diabetes. We aimed to define patient characteristics to guide the decision to test for MODY in youth with diabetes. Of 4750 patients enrolled in the Diabetes Registry at Texas Children's Hospital between July 2016 and July 2019, we selected ("Study Cohort", n = 350) those with: (1) diabetes diagnosis <25 years, (2) family history of diabetes in three consecutive generations, and (3) absent islet autoantibodies except for GAD65. We retrospectively studied their clinical and biochemical characteristics and available MODY testing results. Cluster analysis was then performed to identify the cluster with highest rate of MODY diagnosis. Patients in the Study Cohort were 3.5 times more likely to have been diagnosed with MODY than in the overall Diabetes Registry (4.6% vs. 1.3%, p < 0.001). The cluster (n = 16) with the highest rate of clinician-diagnosed MODY (25%, n = 4/16) had the lowest age (10.9 ± 2.5 year), BMI-z score (0.5 ± 0.9), C-peptide level (1.5 ± 1.2 ng/ml) and acanthosis nigricans frequency (12.5%) at diabetes diagnosis (all p < 0.05). In this cluster, three out of five patients who underwent MODY genetic testing had a pathogenic variant. Using a stepwise approach, we identified that younger age, lower BMI, lower C-peptide, and absence of acanthosis nigricans increase likelihood of MODY in racially/ethnically diverse children with diabetes who have a multigenerational family history of diabetes and negative islet autoantibodies, and can be used by clinicians to select patients for MODY testing.
Substances chimiques
Autoantibodies
0
C-Peptide
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
447-456Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care. 2011;34(8):1878-1884.
Hattersley AT, Greeley SAW, Polak M, et al. ISPAD clinical practice consensus guidelines 2018: the diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2018;19(S27):47-63.
Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010;53(12):2504-2508.
Chung WK, Erion K, Florez JC, et al. Precision medicine in diabetes: a consensus report from the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetologia. 2020;63(9):1671-1693.
Riddle MC, Philipson LH, Rich SS, et al. Monogenic diabetes: from genetic insights to population-based precision in care. Reflections from a diabetes care editors' expert forum. Diabetes Care. 2020;43(12):3117.
Stride A, Stride A, Shields B, et al. Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia. Diabetologia. 2014;57(1):54-56.
Steele AM, Shields BM, Wensley KJ, Colclough K, Ellard S, Hattersley AT. Prevalence of vascular complications among patients with Glucokinase mutations and prolonged, mild hyperglycemia. JAMA. 2014;311(3):279-286.
Shepherd M. Genetic testing in maturity onset diabetes of the young (MODY) - practical guidelines for professionals. Pract Diabetes Int. 2003;20(3):108-110.
Clissold RL, Hamilton AJ, Hattersley AT, Ellard S, Bingham C. HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. Nat Rev Nephrol. 2015;11(2):102-112.
GoodSmith MS, Skandari MR, Huang ES, Naylor RN. The impact of biomarker screening and Cascade genetic testing on the cost-effectiveness of MODY genetic testing. Diabetes Care. 2019;42(12):2247-2255.
Johnson SR, Carter HE, Leo P, et al. Cost-effectiveness analysis of routine screening using massively parallel sequencing for maturity-onset diabetes of the young in a pediatric diabetes cohort: reduced health system costs and improved patient quality of life. Diabetes Care. 2019;42(1):69-76.
Naylor RN, John PM, Winn AN, et al. Cost-effectiveness of MODY genetic testing: translating genomic advances into practical health applications. Diabetes Care. 2014;37(1):202-209.
Kleinberger JW, Copeland KC, Gandica RG, et al. Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med. 2018;20(6):583-590.
Passanisi S, Salzano G, Bombaci B, Lombardo F. Clinical and genetic features of maturity-onset diabetes of the young in pediatric patients: a 12-year monocentric experience. Diabetol Metab Syndr. 2021;13(1):96.
Monogenic diabetes in youth with presumed type 2 diabetes: results from the progress in diabetes genetics in youth (ProDiGY) Collaboration Diabetes Care 2021;44:2312-2319.
Pihoker C, Gilliam LK, Ellard S, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and Glucokinase: results from the SEARCH for diabetes in youth. J Clin Endocrinol Metab. 2013;98(10):4055-4062.
Shepherd M, Shields B, Hammersley S, et al. Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatric diabetes population with monogenic diabetes. Diabetes Care. 2016;39(11):1879-1888.
Carlsson A, Shepherd M, Ellard S, et al. Absence of islet autoantibodies and modestly raised glucose values at diabetes diagnosis should lead to testing for MODY: lessons from a 5-year pediatric Swedish National Cohort Study. Diabetes Care. 2020;43(1):82-89.
Ellard S, Colclough K, Patel KA, Hattersley AT. Prediction algorithms: pitfalls in interpreting genetic variants of autosomal dominant monogenic diabetes. J Clin Invest. 2020;130(1):14-16.
Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, Hattersley AT. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia. 2012;55(5):1265-1272.
Naylor R, Philipson LH. Who should have genetic testing for maturity-onset diabetes of the young? Clin Endocrinol (Oxford). 2011;75(4):422-426.
Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic [beta]-cell diabetes. Nat Clin Pract Endocrinol Metab. 2008;4(4):200.
Donath X, Saint-Martin C, Dubois-Laforgue D, et al. Next-generation sequencing identifies monogenic diabetes in 16% of patients with late adolescence/adult-onset diabetes selected on a clinical basis: a cross-sectional analysis. BMC Med. 2019;17(1):132.
McDonald TJ, Colclough K, Brown R, et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes. Diabet Med. 2011;28(9):1028-1033.
Urbanová J, Rypáčková B, Procházková Z, et al. Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1clevel. Diabet Med. 2014;31(4):466-471.
Fineberg SE, Galloway JA, Fineberg NS, Rathbun MJ, Hufferd S. Immunogenicity of recombinant DNA human insulin. Diabetologia. 1983;25(6):465-469.
Ward JH. Hierarchical grouping to optimize an objective function. J Am Stat Assoc. 1963;58(301):236-244.
Calinski T, Harabasz J. A dendrite method for cluster analysis. Commun Stat Simul Comput. 1974;3(1):1-27.
Duda RO, Hart PE, Stork DG. Pattern Classification. John Wiley & Sons; 2007, pp. xx + 654, ISBN: 0-471-05669-3:305-307.
StataCorp. Stata Statistical Software: Release 15. StataCorp LLC; 2017.
Acosta-Cazares B, Acuin C, Aekplakorn W, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. The Lancet (Br Ed). 2017;390(10113):2627-2642.
Dabelea D, Mayer-Davis EJ, Saydah S, et al. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA. 2014;311(17):1778-1786.
Porter JR, Rangasami JJ, Ellard S, et al. Asian MODY: are we missing an important diagnosis? Diabet Med. 2006;23(11):1257-1260.
Siller AF, Tosur M, Relan S, et al. Challenges in the diagnosis of diabetes type in pediatrics. Pediatr Diabetes. 2020;21(7):1064-1073.
Pinelli M, Acquaviva F, Barbetti F, et al. Identification of candidate children for maturity-onset diabetes of the young type 2 (MODY2) gene testing: a seven-item clinical flowchart (7-iF). PLoS ONE. 2013;8(11):e79933.
Malikova J, Kaci A, Dusatkova P, et al. Functional analyses of HNF1A-MODY variants refine the interpretation of identified sequence variants. J Clin Endocrinol Metab. 2020;105(4):e1377-e1386.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424.
Stanik J, Stanik J, Dusatkova P, et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia. 2014;57(3):480-484.