Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young.
OBJECTIVE: Misdiagnosis of maturity-onset diabetes of the young (MODY) remains widespread, despite the benefits of optimized management. This cross-sectional study examined diagnostic misclassification of MODY in subjects with clinically labeled young adult-onset type 1 and type 2 diabetes by extend...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1797085124305616896 |
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| author | Thanabalasingham, G Pal, A Selwood, M Dudley, C Fisher, K Bingley, P Ellard, S Farmer, A McCarthy, M Owen, K |
| author_facet | Thanabalasingham, G Pal, A Selwood, M Dudley, C Fisher, K Bingley, P Ellard, S Farmer, A McCarthy, M Owen, K |
| author_sort | Thanabalasingham, G |
| collection | OXFORD |
| description | OBJECTIVE: Misdiagnosis of maturity-onset diabetes of the young (MODY) remains widespread, despite the benefits of optimized management. This cross-sectional study examined diagnostic misclassification of MODY in subjects with clinically labeled young adult-onset type 1 and type 2 diabetes by extending genetic testing beyond current guidelines. RESEARCH DESIGN AND METHODS: Individuals were selected for diagnostic sequencing if they displayed features atypical for their diagnostic label. From 247 case subjects with clinically labeled type 1 diabetes, we sequenced hepatocyte nuclear factor 1 α (HNF1A) and hepatocyte nuclear factor 4 α (HNF4A) in 20 with residual β-cell function ≥ 3 years from diagnosis (random or glucagon-stimulated C-peptide ≥ 0.2 nmol/L). From 322 with clinically labeled type 2 diabetes, we sequenced HNF1A and HNF4A in 80 with diabetes diagnosed ≤ 30 years and/or diabetes diagnosed ≤ 45 years without metabolic syndrome. We also sequenced the glucokinase (GCK) in 40 subjects with mild fasting hyperglycemia. RESULTS: In the type 1 diabetic group, two HNF1A mutations were found (0.8% prevalence). In type 2 diabetic subjects, 10 HNF1A, two HNF4A, and one GCK mutation were identified (4.0%). Only 47% of MODY case subjects identified met current guidelines for diagnostic sequencing. Follow-up revealed a further 12 mutation carriers among relatives. Twenty-seven percent of newly identified MODY subjects changed treatment, all with improved glycemic control (HbA(1c) 8.8 vs. 7.3% at 3 months; P = 0.02). CONCLUSIONS: The systematic use of widened diagnostic testing criteria doubled the numbers of MODY case subjects identified compared with current clinical practice. The yield was greatest in young adult-onset type 2 diabetes. We recommend that all patients diagnosed before age 30 and with presence of C-peptide at 3 years' duration are considered for molecular diagnostic analysis. |
| first_indexed | 2024-03-07T02:04:40Z |
| format | Journal article |
| id | oxford-uuid:9e8f9bd3-e98f-453a-a641-c4576d13578f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:04:40Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:9e8f9bd3-e98f-453a-a641-c4576d13578f2022-03-27T00:51:03ZSystematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9e8f9bd3-e98f-453a-a641-c4576d13578fEnglishSymplectic Elements at Oxford2012Thanabalasingham, GPal, ASelwood, MDudley, CFisher, KBingley, PEllard, SFarmer, AMcCarthy, MOwen, KOBJECTIVE: Misdiagnosis of maturity-onset diabetes of the young (MODY) remains widespread, despite the benefits of optimized management. This cross-sectional study examined diagnostic misclassification of MODY in subjects with clinically labeled young adult-onset type 1 and type 2 diabetes by extending genetic testing beyond current guidelines. RESEARCH DESIGN AND METHODS: Individuals were selected for diagnostic sequencing if they displayed features atypical for their diagnostic label. From 247 case subjects with clinically labeled type 1 diabetes, we sequenced hepatocyte nuclear factor 1 α (HNF1A) and hepatocyte nuclear factor 4 α (HNF4A) in 20 with residual β-cell function ≥ 3 years from diagnosis (random or glucagon-stimulated C-peptide ≥ 0.2 nmol/L). From 322 with clinically labeled type 2 diabetes, we sequenced HNF1A and HNF4A in 80 with diabetes diagnosed ≤ 30 years and/or diabetes diagnosed ≤ 45 years without metabolic syndrome. We also sequenced the glucokinase (GCK) in 40 subjects with mild fasting hyperglycemia. RESULTS: In the type 1 diabetic group, two HNF1A mutations were found (0.8% prevalence). In type 2 diabetic subjects, 10 HNF1A, two HNF4A, and one GCK mutation were identified (4.0%). Only 47% of MODY case subjects identified met current guidelines for diagnostic sequencing. Follow-up revealed a further 12 mutation carriers among relatives. Twenty-seven percent of newly identified MODY subjects changed treatment, all with improved glycemic control (HbA(1c) 8.8 vs. 7.3% at 3 months; P = 0.02). CONCLUSIONS: The systematic use of widened diagnostic testing criteria doubled the numbers of MODY case subjects identified compared with current clinical practice. The yield was greatest in young adult-onset type 2 diabetes. We recommend that all patients diagnosed before age 30 and with presence of C-peptide at 3 years' duration are considered for molecular diagnostic analysis. |
| spellingShingle | Thanabalasingham, G Pal, A Selwood, M Dudley, C Fisher, K Bingley, P Ellard, S Farmer, A McCarthy, M Owen, K Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. |
| title | Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. |
| title_full | Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. |
| title_fullStr | Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. |
| title_full_unstemmed | Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. |
| title_short | Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. |
| title_sort | systematic assessment of etiology in adults with a clinical diagnosis of young onset type 2 diabetes is a successful strategy for identifying maturity onset diabetes of the young |
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