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

A Vigo,J.S Pankow,C.M Ballantyne,M.I Schmidt,G Heiss,B.B Duncan,D Couper

doi:10.1590/s0100-879x2006005000121

Abstract

To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (>or=1 U/mL) was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P <or= 0.02), were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95%CI = 0.55, 1.96) proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95%CI = 0.58, 2.88) was seen for those in the highest tertile (>or=2.38 U/mL) of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95%CI = 3.4, 28.5). In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

Highlights

Glutamic acid decarboxylase antibodies (GADA) are present in most patients with autoimmune diabetes at or before diagnosis and are related to insulin secretion abnormalities and to the onset of type 1 diabetes [1]
The objectives of the present study were to characterize the importance of GADA positivity in a representative sample of initially non-diabetic middle-aged individuals enrolled in the Atherosclerosis Risk in Communities (ARIC) Study
We aimed to describe the frequency and correlates of GADA positivity, to evaluate whether GADA positivity predicts the development of diabetes, and to evaluate whether risk factors for diabetes and the early clinical course of diabetes are similar in GADA-positive and GADA-negative individuals

Summary

Introduction

Glutamic acid decarboxylase antibodies (GADA) are present in most patients with autoimmune diabetes at or before diagnosis and are related to insulin secretion abnormalities and to the onset of type 1 diabetes [1]. Most studies to date have evaluated individuals at or after diagnosis of diabetes, and little attention has been directed to the question of whether the presence of GADA predicts the development of diabetes in middle-aged adults. Subclinical inflammation has been found to predict the development of diabetes with onset in middle age [10]. This association is in great part related to obesity, it is logical to inquire whether it reflects the fact that some incident, middle-aged cases may have a subclinical, chronic autoimmune disease affecting ß cells. We aimed to describe the frequency and correlates of GADA positivity, to evaluate whether GADA positivity predicts the development of diabetes, and to evaluate whether risk factors (including inflammation markers) for diabetes and the early clinical course of diabetes are similar in GADA-positive and GADA-negative individuals

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