Islet Cell Associated Autoantibodies and C-Peptide Levels in Patients with Diabetes and Symptoms of Gastroparesis.

Elias S Siraj,Frank Hamilton,James Tonascia,Linda Nguyen,William L Hasler,Gianrico Farrugia,Ajay D Rao,Carol Homko,William J Snape,John Clarke,Laura A Wilson,Irene Sarosiek,Kenneth L Koch,Patrick May,Thomas L Abell,Richard W Mccallum,Jorge Calles,Henry P Parkman,Pankaj J Pasricha

doi:10.3389/fendo.2018.00032

Abstract

Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA). To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity. 113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide. Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients (p = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying (p = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying (p = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide. GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity. NCT01696747.

Highlights

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder and decreased beta-cell function, whereas Type 2 diabetes (T2DM) results from a combination of insulin resistance and diminished beta-cell function
A total of 203 patients with diabetes (113 patients with T1DM and 90 patients with T2DM) having symptoms suggestive of gastroparesis from the NIDDK Gastroparesis Registry (GpR) were assessed in this study
T2DM patients were older, had higher BMI, and less often used insulin compared to T1DM patients

Summary

Introduction

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder (with evidence of autoantibodies) and decreased beta-cell function (measured using C-peptide levels), whereas Type 2 diabetes (T2DM) results from a combination of insulin resistance and diminished beta-cell function. Some patients with T2DM are found to have positive autoantibody profile [often positive glutamic acid decarboxylase-65 antibody (GADA)] suggesting they may have latent autoimmune diabetes in adults (LADA) [1]. In studies specific to North America, LADA has been reported in 3–20% of patients initially thought to have T2DM [2, 3]. The presence of LADA in patients clinically considered to have T2DM at diagnosis is found to be associated with a progression to beta-cell failure requiring insulin within few years [4]. Individuals with LADA have worse glycemic control than patients with T2DM [5]. It has been reported that LADA patients may have a higher prevalence of complications, retinopathy and nephropathy than T2DM [4]

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