Clinical, immunological, and genetic heterogeneity of diabetes in an Italian population-based cohort of lean newly diagnosed patients aged 30-54 years. Piedmont Study Group for Diabetes Epidemiology.
OBJECTIVE
In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients.


METHODS
A population-based cohort of 130 lean (BMI < 25 kg/m2) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-GAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis.


RESULTS
A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA+ and anti-GAD+, with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-GAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% Cl 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-GAD antibodies. Frequencies of adult-onset type 1 and type 2 diabetes were, respectively, 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients.


CONCLUSIONS
Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.
Bruno
G
G
Department of Internal Medicine, University of Turin, Italy.
De Salvia
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Arcari
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Borra
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Grosso
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Carta
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Trovati
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Veglio
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Pagano
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D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000032:analysis; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000097:blood; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D015994:Incidence; D007515:Islets of Langerhans / Q000276:immunology; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D013851:Thinness
D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; C024211:islet cell antibody