PMID- 21518407
OWN - NLM
STAT- MEDLINE
DCOM- 20110818
LR  - 20221207
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 12
IP  - 3 Pt 1
DP  - 2011 May
TI  - Persistently autoantibody negative (PAN) type 1 diabetes mellitus in children.
PG  - 142-9
LID - 10.1111/j.1399-5448.2010.00681.x [doi]
AB  - BACKGROUND: Autoantibody-negative children diagnosed with type 1 diabetes might 
      have unrecognized monogenic or type 2 diabetes. RESEARCH DESIGN AND METHODS: At 
      diagnosis of type 1 diabetes (between ages 0.5 and 16.3 yr, n = 470), 
      autoantibodies [glutamic acid decarboxylase (GAD), insulinoma-associated protein 
      2 (IA2), insulin autoantibodies (IAA), and/or islet cell antibody (ICA)] were 
      positive (ab+) in 330 and negative in 37 (unknown in 103). Autoantibody-negative 
      patients were retested at median diabetes duration of 3.2 yr (range 0.9-16.2) for 
      autoantibodies (GAD, IA2, ZnT8), human leukocyte antigen (HLA) typing, 
      non-fasting C-peptide, and sequencing of HNF4A, HNF1A, KCNJ11, and INS. RESULTS: 
      Nineteen (5% of 367) remained persistently autoantibody negative (PAN), 17 were 
      positive on repeat testing (PORT), and 1 refused retesting. No mutations were 
      found in PORT. One PAN was heterozygous for P112L mutation in HNF1A and 
      transferred from insulin to oral gliclazide. Another PAN transferred to metformin 
      and the diagnosis was revised to type 2 diabetes. The remaining 17 PAN were 
      indistinguishable from the ab+ group by clinical characteristics. HLA genotype 
      was at high risk for type 1 diabetes in 82% of remaining PAN and 100% of PORT. 
      After excluding patients with diabetes duration <1 yr, C-peptide was detectable 
      more frequently in the remaining PAN (7/16) and PORT (6/17) than in a random 
      selection of ab+ (3/28, p = 0.03). CONCLUSIONS: The diagnosis of type 1 diabetes 
      should be reevaluated in PAN patients, because a subset has monogenic or type 2 
      diabetes. The remaining PAN have relatively preserved C-peptide compared with 
      ab+, suggesting slower beta-cell destruction, but a very high frequency of 
      diabetogenic HLA, implying that type 1B (idiopathic) diabetes is rare.
CI  - (c) 2010 John Wiley & Sons A/S.
FAU - Hameed, Shihab
AU  - Hameed S
AD  - Endocrinology, Sydney Children's Hospital, Randwick, NSW, Australia. 
      shihab.hameed@sesiahs.health.nsw.gov.au
FAU - Ellard, Sian
AU  - Ellard S
FAU - Woodhead, Helen J
AU  - Woodhead HJ
FAU - Neville, Kristen A
AU  - Neville KA
FAU - Walker, Jan L
AU  - Walker JL
FAU - Craig, Maria E
AU  - Craig ME
FAU - Armstrong, Taylor
AU  - Armstrong T
FAU - Yu, Liping
AU  - Yu L
FAU - Eisenbarth, George S
AU  - Eisenbarth GS
FAU - Hattersley, Andrew T
AU  - Hattersley AT
FAU - Verge, Charles F
AU  - Verge CF
LA  - eng
PT  - Journal Article
DEP - 20100906
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (Autoantibodies)
RN  - 0 (C-Peptide)
RN  - 0 (HLA Antigens)
RN  - 0 (HNF1A protein, human)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
SB  - IM
CIN - Pediatr Diabetes. 2011 May;12(3 Pt 1):139-41. PMID: 21518406
MH  - Adolescent
MH  - Australia/epidemiology
MH  - Autoantibodies/blood/*immunology
MH  - C-Peptide/blood
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/epidemiology/*genetics/*immunology
MH  - Diabetes Mellitus, Type 2/epidemiology/*genetics/*immunology
MH  - HLA Antigens/genetics/immunology
MH  - Hepatocyte Nuclear Factor 1-alpha/genetics/immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Infant
MH  - Seroepidemiologic Studies
MH  - White People/statistics & numerical data
MH  - Young Adult
EDAT- 2011/04/27 06:00
MHDA- 2011/08/19 06:00
CRDT- 2011/04/27 06:00
PHST- 2011/04/27 06:00 [entrez]
PHST- 2011/04/27 06:00 [pubmed]
PHST- 2011/08/19 06:00 [medline]
AID - 10.1111/j.1399-5448.2010.00681.x [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2011 May;12(3 Pt 1):142-9. doi: 
      10.1111/j.1399-5448.2010.00681.x. Epub 2010 Sep 6.