Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

Vigo, Álvaro; Duncan, Bruce Bartholow; Schmidt, María Inês; Couper, David J.; Heiss, Gerardo; Pankow, James S.; Ballantyne, Christie M.

doi:10.1590/s0100-879x2006005000121

Cited by 6 publications

(5 citation statements)

References 23 publications

(21 reference statements)

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“…In favour of general screening of adult patients with diabetes, patients with Type 2 and LADA cannot be identified by any single clinical feature short of diabetic ketoacidosis. However, the data are conflicting regarding the predictive value of GADA positivity for incident diabetes [14,38,[68][69][70][71].…”

Section: Clinical Presentationmentioning

confidence: 99%

Latent autoimmune diabetes of the adult: current knowledge and uncertainty

Laugesen

Østergaard

Leslie³

2015

Diabet. Med.

152

137

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Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes.What’s new? Latent autoimmune diabetes of the adult (LADA) is an autoimmune diabetes defined by adult-onset, presence of diabetes associated autoantibodies, and no insulin treatment requirement for a period after diagnosis. Immunologically, glutamic acid decarboxylase 65 autoantibodies are by far the most common autoantibody in adult-onset diabetes. LADA is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. LADA shares genetic features with both type 1 and type 2 diabetes. Phenotypically, LADA patients are often misdiagnosed as having type 2 diabetes. LADA patients generally have worse HbA1c levels than type 2 diabetes patients. Clinically, LADA patients tend to have a lower mean age at diabetes onset, lower body mass index and more frequent need for insulin treatment than patients with type 2 diabetes. Management of LADA may require a dedicated strategy, yet currently there is a paucity of randomized controlled trial data.

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Section: Clinical Presentationmentioning

confidence: 99%

Latent autoimmune diabetes of the adult: current knowledge and uncertainty

Laugesen

Østergaard

Leslie³

2015

Diabet. Med.

152

137

View full text Add to dashboard Cite

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“… 12 However, the participants in that study were actually at high risk for diabetes and were not normal adults. The other three studies with negative predictive results in northern Italy, 19 the USA 25 and Sweden 26 are limited by their small GADA + samples. The present study showed that GADA high was associated with a 4.16-fold increased risk, and GADA low was associated with a 2.63-fold increased risk of diabetes among Chinese adults.…”

Section: Discussionmentioning

confidence: 98%

Predictive Value of GAD Antibody for Diabetes in Normal Chinese Adults: A Retrospective Cohort Study in China

Lin

Deng

et al. 2021

DMSO

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Purpose: To investigate the prevalence of GAD antibody (GADA) in the general adult population and to evaluate its predictive value for diabetes in China. Patients and Methods: We searched the PUMCH-HM database and identified 36,731 adult subjects with GADA test results from 2012 to 2015. We then established a retrospective cohort of 4835 nondiabetic subjects at baseline with complete annual health evaluation records through 2019. The median follow-up time was 4.8 (3.0-7.3) years. Results: The overall prevalence of GADA was 0.53% and was higher in diabetic subjects (1.25%) than in nondiabetic subjects (0.47%). We found a decrease in baseline body mass index (BMI) from the GADA-to GADA high subgroups among baseline diabetic and prediabetic patients and also those who developed diabetes later in the cohort study. A total of 136 subjects (2.8%) developed diabetes after a median follow-up of 3.5 years. For GADA + participants, BMI was not associated with the risk for diabetes. In the Cox regression model, the GADA low and GADA high exhibited 2.63-fold and 4.16-fold increased risk for diabetes, respectively. This increased risk for diabetes by GADA-positivity is only found in male adults (HR 4.55, 95% CI 2.25-9.23). Conclusion:GADA has a low prevalence in China but is associated with a 2.63-4.16-fold increased risk for diabetes.

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Section: Discussionmentioning

confidence: 99%

“…Our finding that GAD autoantibody positivity did not predict diabetes incidence is consistent with some , but not all studies . The Atherosclerosis Risk in Communities Study found no excess risk (hazard ratio: 1.04, 95% CI: 0.55–1.96) for GAD autoantibody‐positive participants . In the Cremona Italy study, none of the participants with normal glucose tolerance who were GAD autoantibody‐ and/or insulinoma‐associated‐2 autoantibody‐positive progressed to diabetes over an 8‐year follow‐up .…”

Section: Discussionmentioning

confidence: 99%

Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program

Dabelea

Knowler

et al. 2014

Diabet. Med.

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Aims To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program. Methods A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes. Results The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA1c, estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56–1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%). Conclusions These data suggest that ‘diabetes autoimmunity’, as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes.

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Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

Cited by 6 publications

References 23 publications

Latent autoimmune diabetes of the adult: current knowledge and uncertainty

Latent autoimmune diabetes of the adult: current knowledge and uncertainty

Predictive Value of GAD Antibody for Diabetes in Normal Chinese Adults: A Retrospective Cohort Study in China

Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program

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