OBJECTIVE: Patients with GAD antibodies (GADAb) showing clinical features of type 2 diabetes typically exhibit progression to an insulin-dependent state in several months or years. This condition is diagnosed as slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults, a subtype of adult-onset autoimmune diabetes. However, some patients diagnosed with adult-onset autoimmune diabetes do not progress to an insulin-dependent state. We conducted a retrospective cohort study to identify patients with non-insulin-dependent diabetes among those diagnosed with adult-onset autoimmune diabetes using measurable indicators in routine clinical practice.
METHODS: We surveyed data from the electronic medical records of all patients with GADAb from eight medical centres in Japan for selecting and analysing patients who matched the diagnostic criteria of SPIDDM.
RESULTS: Overall, 345 patients were analysed; of these, 162 initiated insulin therapy (insulin therapy group), whereas 183 did not (non-insulin therapy group) during the follow-up period (median 3.0 years). Patients in the non-insulin therapy group were more likely to be male and presented a later diabetes onset, shorter duration of diabetes, higher BMI, higher blood pressure levels, lower HbA1c levels, lower GADAb levels and lesser antidiabetic agent use than those in the insulin therapy group when GADAb was first identified as positive. A Cox proportional hazards model showed that BMI, HbA1c levels and GADAb levels were independent factors for progression to insulin therapy. Kaplan-Meier analyses revealed that 86.0% of the patients with diabetes having GADAb who presented all three factors (BMI ≥ 22 kg/m2, HbA1c < 75 mmol/mol [9.0%] and GADAb <10.0 U/ml) did not require insulin therapy for 4 years.
CONCLUSIONS: Higher BMI (≥22 kg/m2), lower HbA1c (<75 mmol/mol [9.0%]) and lower GADAb levels (<10.0 U/ml) can predict a non-insulin-dependent state for at least several years in Japanese patients with diabetes having GADAb.

UNASSIGNED: To investigate the prevalence of GAD antibody (GADA) in the general adult population and to evaluate its predictive value for diabetes in China.
UNASSIGNED: 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.
UNASSIGNED: 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 GADAhigh 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 GADAlow and GADAhigh 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).
UNASSIGNED: GADA has a low prevalence in China but is associated with a 2.63-4.16-fold increased risk for diabetes.

BACKGROUND: The glutamic acid decarboxylase antibody (GADA) test, commonly used to diagnose autoimmune diabetes, is not cost-effective in areas of low prevalence. The aim of this study was to develop a convenient tool to discriminate adult-onset GADA-positive autoimmune diabetes from type 2 diabetes (T2DM) in patients with newly diagnosed diabetes.
METHODS: This retrospective cross-sectional study, conducted at Changhua Christian Hospital in Taiwan, collected electronic medical record data from January 2009 to December 2018. Patients were divided into a case group (GADA+, n = 152) and a reference group (T2DM, n = 358). Variables that differed significantly between the groups were subjected to receiver operator characteristic analysis to establish cutoff values. Discriminant function analysis was then employed to discriminate the two groups.
RESULTS: At the onset of diabetes, the GADA+ group was younger, with lower body mass index (BMI), higher hemoglobin A1c (HbA1c), higher high-density lipoprotein cholesterol (HDL-C), and lower total cholesterol and triglycerides (TG). Five major factors were identified to form the linear discriminant functions: BMI, age at onset, TG, HDL-C, and HbA1c. BMI < 23 kg/m2 was the most important factor, followed by TG < 98 mg/dL, HDL-C ≥ 46 mg/dL, age at onset < 30 years, and HbA1c ≥ 8.6%. The overall accuracy of the linear discriminant functions was 87.1%, with 84.2% sensitivity and 88.3% specificity.
CONCLUSIONS: Routine tests in diabetes care were used to establish a convenient, low-cost tool that may assist in the early identification of adult-onset GAD+ autoimmune diabetes in clinical practice.

Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with heterogeneous features. This study aimed to investigate the persistent status of glutamic acid decarboxylase antibody (GADA) in patients with LADA and its association with clinical characteristics.
This 3-year follow-up study enrolled 107 LADA and 40 type 2 diabetes mellitus (T2DM) patients from October 2005 to December 2013. GADA titer, epitopes, and clinical characteristics (including fasting C-peptide and HbA1c ) in LADA patients were assayed annually. The human leukocyte antigen DQ (HLA-DQ) genotypes were also analysed. The relationship between the persistence of GADA and the clinical characteristics was investigated in LADA patients.
After 3-year follow-up, 36.5% (39/107) LADA patients remained GADA positive (persistently positive group), 19.6% (21/107) patients fluctuated positively and negatively (fluctuating group), and 43.9% (47/107) patients became GADA negative, among which 61.7% (29/47) seroconversions occurred within 6 months of follow-up (transiently positive group). The GADA persistently positive group possessed higher titer of GADA than transiently positive group and fluctuant group (all p = 0.000), higher reactivities to middle and C-terminal regions of GAD65 than those in transiently positive group (p = 0.001 and p = 0.000, respectively), and lower baseline fasting C-peptide level than T2DM patients and transiently positive group [415(31-1862) vs 620(220-1658) pmol/L, p = 0.014; and 415(31-1862) vs 705(64-1541) pmol/L, p = 0.017, respectively]. The GADA transiently positive group retained a higher HbA1c level when compared with T2DM patients (p = 0.023). In addition, the three LADA groups shared similar frequencies of HLA-DQ susceptible haplotypes that were higher as compared with T2DM. The GADA persistently positive group had a higher annual declining rate in fasting C-peptide than T2DM patients [-14%(-174-33%) vs -1%(-27-28%), p = 0.007].
The LADA patients with GADA transient positivity account for a large proportion, whose clinical characteristics and HLA-DQ haplotypes are different from those of T2DM. The patients with high titer GADA and reactivities to GADA65 middle and C-terminal regions showed a persistent GADA positivity, in which a worse baseline and accelerated decline of β-cell function need early intervention in the practice. Copyright © 2016 John Wiley & Sons, Ltd.