title: Islet autoantibodies in clinically diagnosed type 2 diabetes: prevalence and relationship with metabolic control (UKPDS 70).
abstract: OBJECTIVE
  We examined the prevalence of islet autoantibodies and their relationship to glycaemic control over 10 years in patients diagnosed clinically with new-onset type 2 diabetes.
  
  
  METHODS
  Patient clinical characteristics and autoantibody status were determined at entry to the UK Prospective Diabetes Study (UKPDS) before randomisation to different glucose control policies. Patients were followed for 10 years.
  
  
  RESULTS
  Data available on 4,545 of the 5,102 UKPDS patients showed that 11.6% had antibodies to at least one of three antigens: islet cell cytoplasm, glutamic acid decarboxylase and islet autoantibody 2A (IA-2A). Autoantibody-positive patients were younger, more often Caucasian and leaner, with lower beta cell function and higher insulin sensitivity than autoantibody-negative patients. They also had higher HbA1c, and HDL-cholesterol levels, and lower blood pressure, total cholesterol and plasma triglyceride levels. Despite relative hyperglycaemia, autoantibody-positive patients were less likely to have the metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Program III), reflecting a more beneficial overall risk factor profile. Of 3,867 patients with post-dietary run-in fasting plasma glucose (FPG) values between 6.0 and 14.9 mmol/l and no hyperglycaemic symptoms, 9.4% were autoantibody-positive, compared with 25.1% of 678 patients with FPG values of 15.0 mmol/l or higher, or hyperglycaemic symptoms. In both groups, no differences were seen between those with and without autoantibodies in changes to HbA1c over time, but autoantibody-positive patients required insulin treatment earlier, irrespective of the allocated therapy (p<0.0001).
  
  
  CONCLUSIONS
  Autoantibody-positive patients can be treated initially with sulphonylurea, but are likely to require insulin earlier than autoantibody-negative patients.
authors.affiliation: University of Western Australia, School of Medicine and Pharmacology, Fremantle Hospital, P.O. Box 480, Fremantle, Western Australia, 6959, Australia.
authors.forename: T M E
authors.initials: TM
authors.lastname: Davis
authors.forename: A D
authors.initials: AD
authors.lastname: Wright
authors.forename: Z M
authors.initials: ZM
authors.lastname: Mehta
authors.forename: C A
authors.initials: CA
authors.lastname: Cull
authors.forename: I M
authors.initials: IM
authors.lastname: Stratton
authors.forename: G F
authors.initials: GF
authors.lastname: Bottazzo
authors.forename: E
authors.initials: E
authors.lastname: Bosi
authors.forename: I R
authors.initials: IR
authors.lastname: Mackay
authors.forename: R R
authors.initials: RR
authors.lastname: Holman
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001786:Blood Glucose / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D004035:Diet Therapy; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000276:immunology / Q000628:therapy; D007328:Insulin / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002784:Cholesterol; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin; D008074:Lipoproteins; D013453:Sulfonylurea Compounds; C096322:ICA512 autoantibody; C024211:islet cell antibody
references.citation: Diabet Med. 2000 Sep;17 (9):667-74
references.pmid: 11051287
references.citation: Diabetologia. 1991 Dec;34(12 ):877-90
references.pmid: 1778353
references.citation: Lancet. 1990 Jan 20;335(8682):147-9
references.pmid: 1967440
references.citation: Ann Intern Med. 1998 Feb 1;128(3):165-75
references.pmid: 9454524
references.citation: Diabetes Care. 1998 Dec;21(12):2191-2
references.pmid: 9839117
references.citation: Diabetes Care. 2003 Oct;26(10):2954-6
references.pmid: 14514609
references.citation: Diabetes. 2003 May;52(5):1128-36
references.pmid: 12716742
references.citation: Lancet. 1998 Sep 12;352(9131):837-53
references.pmid: 9742976
references.citation: BMJ. 1998 Mar 14;316(7134):823-8
references.pmid: 9549452
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: Diabetes Care. 1996 Jan;19(1):60-3
references.pmid: 8720536
references.citation: Diabetes. 1999 Jan;48(1):150-7
references.pmid: 9892237
references.citation: Diabetes. 1998 Dec;47(12):1857-66
references.pmid: 9836516
references.citation: Diabet Med. 1994 Jul;11(6):534-44
references.pmid: 7955969
references.citation: J Immunol. 1998 Sep 1;161(5):2648-54
references.pmid: 9725268
references.citation: BMJ. 2000 Aug 12;321(7258):405-12
references.pmid: 10938048
references.citation: J Immunol. 1995 Dec 1;155(11):5419-26
references.pmid: 7594559
references.citation: Diabetes Res Clin Pract. 1996 Jul;33(2):89-97
references.pmid: 8879963
references.citation: Diabetes. 1993 Feb;42(2):359-62
references.pmid: 8425674
references.citation: Diabetes Care. 2003 Feb;26(2):452-7
references.pmid: 12547879
references.citation: Diabetes Care. 1995 Dec;18(12):1557-65
references.pmid: 8722051
references.citation: Diabetologia. 2001 Aug;44(8):1005-10
references.pmid: 11484077
references.citation: Diabetologia. 1985 Jul;28(7):412-9
references.pmid: 3899825