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.

Bruno, Graziella; Salvia, Alberto De; Arcari, R.; Borra, M; Grosso, N. Del; Carta, Q; Trovati, Mariella; Veglio, M; Pagano, G

doi:10.2337/diacare.22.1.50

Cited by 26 publications

(23 citation statements)

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“…Unfortunately, only few large studies have characterised antibody-positive diabetes in both young and middle-aged patients [11,14,15]. Also, to date, diagnosis of type 2 diabetes has been by exclusion, with patients not presenting with genetic and autoimmune markers of type 1 diabetes being considered to have type 2 diabetes [3,11,16,17].…”

Section: Introductionmentioning

confidence: 99%

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

et al. 2008

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Aims/hypothesis Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients.Methods In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. Results Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p=9.4×10 −34 ; 45% vs 18%, p=1.4×10 −16 ), PTPN22 CT/TT (34% vs 26%, p=0.0023; 31% vs 23%, p=0.034), INS VNTR class I/I (69% vs 53%, p=1.3×10 −8 ; 69% vs 51%, p=8.5×10 −5 ) and INS VNTR class IIIA/IIIA (75% vs 63%, p= 4.3×10 −6 ; 73% vs 60%, p=0.008) was increased in young and middle-aged GAD antibodies (GADA)-Diabetologia

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Section: Introductionmentioning

confidence: 99%

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

et al. 2008

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“…Another Swedish study (32) reported that the prevalence of GAD antibodies was 8% overall in newly diagnosed diabetic patients and only 3.2% in patients classified as having type 2 diabetes. A Dutch population-based study (33) found GAD antibody positivity in 3.5% (95% CI 0.7-10%) of patients already known to have diabetes (type 1 or type 2), whereas, although different criteria were used, a higher prevalence of GAD positivity (Ͼ20%) was observed in Northern Italy (34). In the U.K.…”

Section: Immune Markersmentioning

confidence: 99%

Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)

2001

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Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting β-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.

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“…The proportion of LADA among those patients attending diabetes clinics has been investigated in two previous studies in Italy; one performed in a subset of lean diabetic patients (13) and the other at a single institution (14).…”

Section: Introductionmentioning

confidence: 99%

Clinical phenotype and β-cell autoimmunity in Italian patients with adult-onset diabetes

et al. 2006

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Objective: To characterize the phenotype of a large population of Italian patients with adult onset ($ 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 IA2b/phogrin (IA-2bA). Design and methods: This was a cross-sectional study comprising a total of 881 patients, aged # 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-2bA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2b. 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-2bA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2bA, 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 # 10 units; P , 0.007). Conclusions: Patients with adult onset diabetes characterized by autoimmunity to b-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 b-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings. European Journal of Endocrinology 154 441-447

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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.

Cited by 26 publications

References 0 publications

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)

Clinical phenotype and β-cell autoimmunity in Italian patients with adult-onset diabetes

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