Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes.
OBJECTIVE
To characterize the phenotype of a large population of Italian patients with adult onset (> or =40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA).


METHODS
This was a cross-sectional study comprising a total of 881 patients, aged < or = 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; s.d.) years. GADA, IA-2A and IA-2betaA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2beta. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies.


RESULTS
Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2betaA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2betaA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P < 0.009), had higher glycated haemoglobin (Hb A1c) (P < 0.001), lower body mass index (BMI; P < 0.0005) and waist/hip ratio (WHR; P < 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend < 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with > 10 units vs 42.0% in those with < or = 10 units; P < 0.007).


CONCLUSIONS
Patients with adult onset diabetes characterized by autoimmunity to beta-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and beta-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings.
Genovese
S
S
Endocrinology and Diabetes Unit and Biometrical Unit, Istituto Clinico Humanitas IRCCS, Rozzano, Milan, Italy. stefano.genovese@humanitas.it
Bazzigaluppi
E
E
Gonçalves
D
D
Ciucci
A
A
Cavallo
M G
MG
Purrello
F
F
Anello
M
M
Rotella
C M
CM
Bardini
G
G
Vaccaro
O
O
Riccardi
G
G
Travaglini
P
P
Morenghi
E
E
Bosi
E
E
Pozzilli
P
P
D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000032:analysis; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology*; D007558:Italy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000276:immunology / Q000378:metabolism; D049629:Waist-Hip Ratio
D001323:Autoantibodies; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D017027:Protein Tyrosine Phosphatases