Phenotypic Characteristics of GAD Antibody-Positive Recently Diagnosed Patients With Type 2 Diabetes in North America and Europe

Zinman, Bernard; Kahn, Steven E.; Haffner, Steven M.; O'Neill, Mark; Heise, Mark; Freed, Martin I.

doi:10.2337/diabetes.53.12.3193

Cited by 166 publications

(144 citation statements)

References 25 publications

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“…In our cohort, indeed, we found, on the one hand, a worse metabolic control and, on the other, a lower prevalence of markers of metabolic syndrome in autoantibody-positive type 2 diabetic patients. These phenotypic differences might be predictive of differences in the clinical outcome of patients with an adult onset of diabetes (31,33). A higher HbA1c level found in patients with autoimmune diabetes is a finding indicating that therapy in these patients is probably inappropriate.…”

Section: Discussionmentioning

confidence: 95%

“…In a recent study performed in a large cohort of patients with type 2 diabetes, the prevalence of the metabolic syndrome was lower in GADA-positive patients in comparison with those without autoantibodies (31). In the Botnia study (32), indicators of metabolic syndrome such as increased body weight, central obesity (by means of WHR), hypertension and dyslipidaemia were GADA titre (%) Figure 4 Prevalence of patients treated with insulin in relation to the GADA titre.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…In general, LADA differs from type 2 diabetes in terms of metabolic syndrome, genetic characteristics, and the progression to insulin requirement (2)(3)(4)(5)(6). However, some patients show features similar to type 2 diabetes, which characterize a distinct form, LADA type 2 (7) or type 1.5 diabetes (8).…”

Section: Anti-gad Antibody Titers In Ladamentioning

confidence: 99%

“…Antibodies are the main predictors of functional deterioration of beta cells (2), especially at high titers (2,4,7,9) and when present in combination (GADA and ICA) (3,6,7). A prospective multicenter study has shown that patients with LADA benefit from early insulinization, but this gain was restricted to those with high GADA titers and who still presented a good functional reserve of beta cells (10,11).…”

Section: Anti-gad Antibody Titers In Ladamentioning

confidence: 99%

Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization

Rosário

Reis

Fagundes

et al. 2007

Arq Bras Endocrinol Metab

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Objective: To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers). Methods: Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis. Results: Insulin resistance was higher in the GADA-group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA-or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later. Conclusion: We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

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“…Recent large studies indicate that the proportion (7-10%) of adult-onset diabetic patients who have autoimmune diabetes, including LADA, is such that this is the most prevalent form of autoimmune type 1 diabetes (1,2). Nonetheless, we know little of the natural history of this form of autoimmune diabetes.…”

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confidence: 99%

LADA and CARDS: A Prospective Study of Clinical Outcome in Established Adult-Onset Autoimmune Diabetes

et al. 2014

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OBJECTIVEDiabetes-associated autoantibodies can be detected in adult-onset diabetes, even when initially non-insulin requiring, i.e., with latent autoimmune diabetes. We aimed to identify adult-onset autoimmune diabetes in patients with established "type 2 diabetes" participating in the Collaborative Atorvastatin Diabetes Study (CARDS) to characterize their phenotype and clinical outcome. RESEARCH DESIGN AND METHODSWe prospectively studied 2,425 European patients with presumed type 2 diabetes (mean age 62 years, diabetes duration 7.9 years) for outcomes at 3.9 years after randomization to either atorvastatin or placebo. Subjects were screened for autoantibodies to GAD (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc-transporter 8 (ZnT8A). RESULTSA total of 173 patients (7.1%) had GADA, of whom 11 (0.5%) and 5 (0.2%) were also positive for IA-2A and ZnT8A, respectively. At baseline, 44% of GADA-positive patients were not on insulin. Fewer autoantibody-positive than autoantibodynegative patients had metabolic syndrome (64 vs. 80%), and more were on insulin (56 vs. 17%) (P < 0.0001 for each) without lower HbA 1c (69 mmol/mol [8.5%] vs. 62 mmol/mol [7.8%]). The frequency of microvascular and macrovascular events was similar in both cohorts, independent of atorvastatin.

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Phenotypic Characteristics of GAD Antibody-Positive Recently Diagnosed Patients With Type 2 Diabetes in North America and Europe

Cited by 166 publications

References 25 publications

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

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

Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization

LADA and CARDS: A Prospective Study of Clinical Outcome in Established Adult-Onset Autoimmune Diabetes

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