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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
Lund Univ, Sweden.
Univ Exeter, England.
Univ Exeter, England; Royal Devon and Exeter NHS Fdn Trust, England.
Univ Exeter, England.
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2020 (Engelska)Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, nr 1, s. 82-89Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.

RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCKHNF1A, and HNF4A, through either routine clinical or research testing.

RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment.

CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.

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Arlington, VA, United States: American Diabetes Association , 2020. Vol. 43, nr 1, s. 82-89
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
URN: urn:nbn:se:liu:diva-163462DOI: 10.2337/dc19-0747ISI: 000508573600023PubMedID: 31704690Scopus ID: 2-s2.0-85077016348OAI: oai:DiVA.org:liu-163462DiVA, id: diva2:1393691
Anmärkning

Funding Agencies|Swedish Child Diabetes Foundation; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK-063861]; National Institute for Health Research (U.K.)National Institute for Health Research (NIHR); Wellcome TrustWellcome Trust; Wellcome TrustWellcome Trust [098395/Z/12/Z]

Tillgänglig från: 2020-02-17 Skapad: 2020-02-17 Senast uppdaterad: 2021-05-05Bibliografiskt granskad

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Samuelsson, UlfLudvigsson, Johnny

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