High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7)

Abstract

Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P!0.0001 for both). A BMI of %25 kg/m 2 and IA-2 IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P!0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P!0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P!0.0001, ORZ6.95). Conclusions: High GADA titer, BMI % 25, ZnT8 and IA-2 IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.

Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes

“…Although control with oral agents is possible for a variable period of time, these individuals, who are typically but not always lean, develop insulin requirements faster than those with typical type 2 diabetes [57] and progressively manifest metabolic changes similar to those seen in type 1 diabetes. Ultimately, they are optimally treated with a regimen consisting of multiple daily injections of insulin, ideally using a basal-bolus approach (or an insulin pump).…”

Autoimmunity plays a role in the onset of diabetes after 40 years of age

“…Although the pathogenesis of type 2 diabetes is thought to be different from that of type 1 diabetes, there may be some overlap; however, the evidence for this is limited [3]. Associations of beta cell autoimmunity, as assessed by presence of GAD65 antibodies, with insulin requirement and diabetes complications have been investigated in prevalent adult-onset diabetes [4][5][6][7][8][9][10][11][12][13][14]. In contrast, there are only a few population-based prospective studies exploring the association between autoimmunity and incident diabetes.…”

Identification of autoimmune type 1 diabetes and multiple organ‐specific autoantibodies in adult‐onset non‐insulin‐requiring diabetes in China: A population‐based multicentre nationwide survey

“…Assessment of GAD, IA2 and Znt8 autoantibodies in white people has identified ~10% of people with T2D as having ADM . Importantly, follow‐up studies found that people with autoantibody‐positive diabetes have a more than fivefold risk of progression to insulin requirement compared with people who are autoantibody‐negative . In addition, ADM may co‐exist with a risk of other organ‐specific autoimmune diseases, including most commonly those involving the thyroid, small intestine and adrenal glands .…”

“…Assessment of GAD, IA2 and Znt8 autoantibodies in white people has identified~10% of people with T2D as having ADM. 7,8 Importantly, follow-up studies found that people with autoantibody-positive diabetes have a more than fivefold risk of progression to insulin requirement compared with people who are autoantibody-negative. [9][10][11] In addition, ADM may co-exist with a risk of other organ-specific autoimmune diseases 12,13 , including most commonly those involving the thyroid, small intestine and adrenal glands. [12][13][14][15][16][17] Finally, the genetic characteristics of people with ADM are more closely related to T1D than T2D in both white and Chinese people, but the latter have fewer high-risk histocompatibility antigen (HLA) alleles than the former.…”