The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study
Georgeanna J Klingensmith, Laura Pyle, Silva Arslanian, Kenneth C Copeland, Leona Cuttler, Francine Kaufman, Lori Laffel, Santica Marcovina, Sherida E Tollefsen, Ruth S Weinstock, Barbara Linder, TODAY Study Group, Georgeanna J Klingensmith, Laura Pyle, Silva Arslanian, Kenneth C Copeland, Leona Cuttler, Francine Kaufman, Lori Laffel, Santica Marcovina, Sherida E Tollefsen, Ruth S Weinstock, Barbara Linder, TODAY Study Group
Abstract
Objective: To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings.
Research design and methods: Children (10-17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations.
Results: Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects.
Conclusions: Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes.
Trial registration: ClinicalTrials.gov NCT00081328.
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References
- Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P: Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996;128(5 Pt 1):608–615
- Dabelea D, Pettitt DJ, Jones KL, Arslanian SA: Type 2 diabetes mellitus in minority children and adolescents. An emerging problem. Endocrinol Metab Clin North Am 1999;28:709–729, viii
- Fagot-Campagna A, Pettitt DJ, Engelgau MM, Burrows NR, Geiss LS, Valdez R, Beckles GL, Saaddine J, Gregg EW, Williamson DF, Narayan KM: Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 2000;136:664–672
- Writing Group for the SEARCH for Diabetes in Youth Study Group Incidence of diabetes in youth in the United States. JAMA 2007;297:2716–2724
- Vehik K, Hamman RF, Lezotte D, Norris JM, Klingensmith G, Bloch C, Rewers M, Dabelea D: Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado youth. Diabetes Care 2007;30:503–509
- Harjutsalo V, Sjöberg L, Tuomilehto J: Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008;371:1777–1782
- Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G: EURODIAB Study Group Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet 2009;373:2027–2033
- Scott CR, Smith JM, Cradock MM, Pihoker C: Characteristics of youth-onset noninsulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus at diagnosis. Pediatrics 1997;100:84–91
- Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ: Changing prevalence of overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care 2003;26:2871–2875
- Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, Shattock M, Bottazzo GF, Holman R: UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997;350:1288–1293
- TODAY Study Group, Zeitler P, Epstein L, Grey M, Hirst K, Kaufman F, Tamborlane W, Wilfley D: Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes 2007;8:74–87
- Diagnosis and classification of diabetes mellitus. Diabetes Care 2004;27(Suppl. 1):S5–S10
- Desai M, Clark A: Autoimmune diabetes in adults: lessons from the UKPDS. Diabet Med 2008;25(Suppl. 2):30–34
- Wenzlau JM, Moua O, Sarkar SA, Yu L, Rewers M, Eisenbarth GS, Davidson HW, Hutton JC: SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann NY Acad Sci 2008;1150:256–259
- Gottschalk M, Danne T, Fuerst-Recktenwald S: Ethnic origin is unrelated to autoimmunity and residual pancreatic function in 471 youth with clinically diagnosed type 2 diabetes. Pediatr Diabetes 2009;10:240–247
- Pozzilli P, Guglielmi C: Double diabetes: a mixture of type 1 and type 2 diabetes in youth. Endocr Dev 2009;14:151–166
- Tfayli H, Bacha F, Gungor N, Arslanian S: Phenotypic type 2 diabetes in obese youth: insulin sensitivity and secretion in islet cell antibody-negative versus -positive patients. Diabetes 2009;58:738–744
- Zinman B, Kahn SE, Haffner SM, O'Neill MC, Heise MA, Freed MI: Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe. Diabetes 2004;53:3193–3200
- Gilliam LK, Brooks-Worrell BM, Palmer JP, Greenbaum CJ, Pihoker C: Autoimmunity and clinical course in children with type 1, type 2, and type 1.5 diabetes. J Autoimmun 2005;25:244–250
Source: PubMed