Sulfonylurea Treatment Before Genetic Testing in Neonatal Diabetes: Pros and Cons
Context:Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes.Objective:Assess the risks and benefits of initiating sulfo...
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| Published in | The journal of clinical endocrinology and metabolism Vol. 99; no. 12; pp. E2709 - E2714 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Oxford University Press
01.12.2014
Copyright by The Endocrine Society Endocrine Society |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-972X 1945-7197 1945-7197 |
| DOI | 10.1210/jc.2014-2494 |
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| Abstract | Context:Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes.Objective:Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available.Design, Setting, and Patients:Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry.Main Outcome Measures:Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically.Results:A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases.Conclusions:Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis. |
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| AbstractList | Context:Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes.Objective:Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available.Design, Setting, and Patients:Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry.Main Outcome Measures:Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically.Results:A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases.Conclusions:Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis. Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes.CONTEXTDiabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes.Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available.OBJECTIVEAssess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available.Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry.DESIGN, SETTING, AND PATIENTSObservational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry.Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically.MAIN OUTCOME MEASURESResponse to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically.A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases.RESULTSA total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases.Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis.CONCLUSIONSSulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis. CONTEXT:Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes. OBJECTIVE:Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available. DESIGN, SETTING, AND PATIENTS:Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry. MAIN OUTCOME MEASURES:Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically. RESULTS:A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases. CONCLUSIONS:Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis. Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes. Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available. Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry. Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically. A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases. Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis. |
| Author | Hwang, Jessica L. Naylor, Rochelle N. Carmody, David Zimmer, Carrie A. Greeley, Siri Atma W. Sima, Daniela I. Felipe, Dania L. Davis, Ajuah O. Philipson, Louis H. Kotlyarevska, Kateryna Bell, Charles D. Dickens, Jazzmyne T. |
| AuthorAffiliation | Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637; Department of Pediatric Endocrinology (D.I.S.), Albany Medical Center Hospital, Albany, New York 12208; Department of Endocrinology and Diabetes (D.L.F.), Louisiana State University Health Sciences Center and Childrenʼs Hospital, New Orleans, Louisiana 70112; Academic Endocrinology and Edward Hospital (C.A.Z.), Naperville, Illinois 60540; Department of Pediatrics (A.O.D.), Division of Pediatric Endocrinology, MetroHealth Medical Center, Cleveland, Ohio 44109; and Nunnelee Pediatric Specialty Clinic (K.K.), Betty H. Cameron Womenʼs and Childrenʼs Hospital, New Hanover Regional Medical Center, Wilmington, North Carolina 28401 |
| AuthorAffiliation_xml | – name: Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637; Department of Pediatric Endocrinology (D.I.S.), Albany Medical Center Hospital, Albany, New York 12208; Department of Endocrinology and Diabetes (D.L.F.), Louisiana State University Health Sciences Center and Childrenʼs Hospital, New Orleans, Louisiana 70112; Academic Endocrinology and Edward Hospital (C.A.Z.), Naperville, Illinois 60540; Department of Pediatrics (A.O.D.), Division of Pediatric Endocrinology, MetroHealth Medical Center, Cleveland, Ohio 44109; and Nunnelee Pediatric Specialty Clinic (K.K.), Betty H. Cameron Womenʼs and Childrenʼs Hospital, New Hanover Regional Medical Center, Wilmington, North Carolina 28401 |
| Author_xml | – sequence: 1 givenname: David surname: Carmody fullname: Carmody, David organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 – sequence: 2 givenname: Charles D. surname: Bell fullname: Bell, Charles D. organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 – sequence: 3 givenname: Jessica L. surname: Hwang fullname: Hwang, Jessica L. organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 – sequence: 4 givenname: Jazzmyne T. surname: Dickens fullname: Dickens, Jazzmyne T. organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 – sequence: 5 givenname: Daniela I. surname: Sima fullname: Sima, Daniela I. organization: 2Department of Pediatric Endocrinology (D.I.S.), Albany Medical Center Hospital, Albany, New York 12208 – sequence: 6 givenname: Dania L. surname: Felipe fullname: Felipe, Dania L. organization: 3Department of Endocrinology and Diabetes (D.L.F.), Louisiana State University Health Sciences Center and Children's Hospital, New Orleans, Louisiana 70112 – sequence: 7 givenname: Carrie A. surname: Zimmer fullname: Zimmer, Carrie A. organization: 4Academic Endocrinology and Edward Hospital (C.A.Z.), Naperville, Illinois 60540 – sequence: 8 givenname: Ajuah O. surname: Davis fullname: Davis, Ajuah O. organization: 5Department of Pediatrics (A.O.D.), Division of Pediatric Endocrinology, MetroHealth Medical Center, Cleveland, Ohio 44109 – sequence: 9 givenname: Kateryna surname: Kotlyarevska fullname: Kotlyarevska, Kateryna organization: 6Nunnelee Pediatric Specialty Clinic (K.K.), Betty H. Cameron Women's and Children's Hospital, New Hanover Regional Medical Center, Wilmington, North Carolina 28401 – sequence: 10 givenname: Rochelle N. surname: Naylor fullname: Naylor, Rochelle N. organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 – sequence: 11 givenname: Louis H. surname: Philipson fullname: Philipson, Louis H. organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 – sequence: 12 givenname: Siri Atma W. surname: Greeley fullname: Greeley, Siri Atma W. email: sgreeley@uchicago.edu organization: 1Departments of Medicine and Pediatrics (D.C., C.D.B., J.L.H., J.T.D., R.N.N., L.H.P., S.A.W.G., Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois 60637 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25238204$$D View this record in MEDLINE/PubMed |
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| Snippet | Context:Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental... CONTEXT:Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental... Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental... |
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| SubjectTerms | Diabetes Diabetes mellitus Diabetes Mellitus, Type 1 - congenital Diabetes Mellitus, Type 1 - diagnosis Diabetes Mellitus, Type 1 - drug therapy Diagnosis Female Genetic screening Genetic testing Genetic Testing - methods Humans Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use Infant Infant, Newborn Insulin JCEM Online: Advances in Genetics Male Mutation Neonates Patients Potassium Channels, Inwardly Rectifying - genetics Retrospective Studies Sulfonylurea Sulfonylurea Compounds - adverse effects Sulfonylurea Compounds - therapeutic use Sulfonylurea Receptors - genetics |
| Title | Sulfonylurea Treatment Before Genetic Testing in Neonatal Diabetes: Pros and Cons |
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