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

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

Abstract

Introduction: 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).

Objective: 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.

Design: 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.

Results: 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.

Conclusion: 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.

Clinicaltrialsgov identifier: NCT01696747.

Keywords: C-peptide; GAD; GAD65; GAD65 antibodies; diabetic gastroparesis; gastric emptying; gastroparesis; islet cell antibodies.

References

    1. Leslie RDG, Kolb H, Schollot NC, Buzzetti R, Mauricio D, De Leiva A, et al. Diabetes classification: grey zones, sound and smoke: action LADA. Diabetes Metab Res Rev (2008) 24:511–9.10.1002/dmrr.877
    1. Zinman B, Kahn SE, Haffner SM, O’Neill MC, Heise MA, Freed MI. Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe. Diabetes (2004) 53:3193–201.10.2337/diabetes.53.12.3193
    1. Hawa MI, Buchan AP, Ola T, Wun CC, DeMicco DA, Bao W, et al. LADA and CARDS: a prospective study of clinical outcome in established adult-onset autoimmune diabetes. Diabetes Care (2014) 37:1643–9.10.2337/dc13-2383
    1. Arikan E, Sabuncu T, Ozer EM, Hatemi H. The clinical characteristics of latent autoimmune diabetes in adults and is relation with chronic complications in metabolically poor controlled Turkish patients with Type 2 diabetes mellitus. J Diabetes Complication (2005) 19:254–8.10.1016/j.jdiacomp.2005.02.004
    1. Andersen CD, Bennet L, Nyström L, Lindblad U, Lindholm E, Groop L, et al. Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy. Diabetologia (2013) 56:252–8.10.1007/s00125-012-2759-y
    1. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology (2004) 127:1592–622.10.1053/j.gastro.2004.09.055
    1. Soota K, Kedar A, Nikitina Y, Arendale E, Vedanarayanan V, Abell TL. Immunomodulation for treatment of drug and device refractory gastroparesis. Results Immunol (2016) 6:11–4.10.1016/j.rinim.2016.02.001
    1. Parkman HP, Yates K, Hasler WL, Nguyen L, Pasricha PJ, Snape WJ, et al. Similarities and differences between diabetic and idiopathic gastroparesis. Clin Gastroenterol Hepatol (2011) 9:1056–64.10.1016/j.cgh.2011.08.013
    1. Pasricha PJ, Colvin R, Yates K, Hasler WL, Abell TL, Ünalp-Arida A, et al. Characteristics of patients with chronic unexplained nausea and vomiting and normal gastric emptying. Clin Gastroenterol Hepatol (2011) 9:567–76.10.1016/j.cgh.2011.03.003
    1. Rentz AM, Kahrilas P, Stanghellini V, Tack J, Talley NJ, de la Loge C, et al. Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders. Qual Life Res (2004) 13:1737–49.10.1007/s11136-004-9567-x
    1. Revicki DA, Rentz AM, Dubois D, Kahrilas P, Stanghellini V, Talley NJ, et al. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther (2003) 18:141–50.10.1046/j.1365-2036.2003.01612.x
    1. Abell TL, Camilleri M, Donohoe K, Hasler WL, Lin HC, Maurer AH, et al. Consensus recommendations for gastric emptying scintigraphy. Am J Gastroenterol (2008) 103:753–63.10.1111/j.1572-0241.2007.01636.x
    1. Koch KL, Hasler WL, Yates KP, Parkman HP, Pasricha PJ, Calles-Escandon J, et al. Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes. Neurogastroenterol Motil (2016) 28(7):1001–15.10.1111/nmo.12800
    1. Liao Y, Xiang Y, Zhou Z. Diagnostic criteria of latent autoimmune diabetes in adults (LADA): a review and reflection. Front Med (2012) 6:243–7.10.1007/s11684-012-0201-y
    1. Singla R, Homko C, Schey R, Parkman HP. Diabetes-related autoantibodies in diabetic gastroparesis. Dig Dis Sci (2015) 60:1733–7.10.1007/s10620-015-3690-0
    1. Balme M, McAllister I, Davis WA, Davis TM. Retinopathy in latent autoimmune diabetes of adults: the Fretmantle Diabetes Study. Diabet Med (2002) 19:602–5.10.1046/j.1464-5491.2002.00739.x
    1. Isomaa B, Almgren P, Henricsson M, Taskinen MR, Tuomi T, Groop L, et al. Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA). Diabetes Care (1999) 22:1347–53.10.2337/diacare.22.8.1347
    1. Li X, Yang L, Zhou Z, Huang G, Yan X. Glutamic acid decarboxylase 65 autoantibody levels discriminate two subtypes of latent autoimmune diabetes in adults. Chin Med J (2003) 116:1728–32.
    1. Owen KR, Stride A, Ellard S, Hattersley AT. Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes. Diabetes Care (2003) 26:2088–93.10.2337/diacare.26.7.2088
    1. Baum P, Herman W, Verlohren HJ, Wagner A, Lohmann T, Grahmann F. Diabetic neuropathy in patients with latent autoimmune diabetes of adults (LADA) compared with patients with type 1 and type 2 diabetes. J Neurol (2003) 250:682–7.10.1007/s00415-003-1055-7
    1. Kleinberger JW, Pollin TI. Undiagnosed MODY: time for action. Curr Diab Rep (2015) 15(12):110.10.1007/s11892-015-0681-7
    1. Homko C, May KP, Siraj E, Rao A, Hamilton C. Islet autoantibodies and C-peptide levels in patients with diabetes and symptoms of gastroparesis. Gastroenterology (2016) 150(4):S718.10.1016/S0016-5085(16)32450-7

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren