Exp Clin Endocrinol Diabetes 2012; 120(07): 428-434
DOI: 10.1055/s-0032-1308979
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Does Glucagon Stimulation Test Help to Predict Autoimmunity in Newly Diagnosed Non Obese Adults with Diabetes?

A. Rogowicz-Frontczak
1   Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland
,
D. Zozulińska-Ziółkiewicz
1   Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland
,
P. Niedźwiecki
1   Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland
,
M. Litwinowicz
1   Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland
,
B. Wierusz-Wysocka
1   Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland
› Author Affiliations
Further Information

Publication History

received 25 October 2011
first decision 06 February 2012

accepted 07 March 2012

Publication Date:
27 April 2012 (online)

Abstract

Aim:

Classification of diabetes type in adults patients remains difficult. This study was undertaken to determine the relationship between presence of autoantibodies in the serum and the result of glucagon stimulation test in non obese patients at aged above 35 years with newly diagnosed diabetes.

Material and methods:

Study involved 52 non obese adults aged 42 years [interquartile range (IQR): 37–46], with body mass index (BMI) 23.7 kg/m2 (IQR: 21.4–26.2). Presence of autoantibodies to islet cells (ICA), antibodies to tyrosine phosphatase (IA-2), glutamic acid decarboxylase autoantibodies (anti-GAD) and plasma fasting and stimulating (6 min after intravenous injection of 1 mg glucagon) C-peptide level was assessed.

Results:

73.1% subjects had at least 1 of 3 assessed autoantibodies, 26.9% patients were autoantibodies negative. According to serum C-peptide concentration after stimulation test with glucagon patients were divided into 2 groups. Receiver Operating Characteristic (ROC) Curve for determination of an optimal cut-point (C-peptide stimulation above and below 1.6) was used. In patients with negative stimulation test higher prevalence of 2 (33.3% vs. 66.7%; p=0.04) or 3 (12.5% vs. 87.5%, p=0.01) positive autoantibodies was noticed in comparison to patients with positive stimulation test. Multivariate logistic regression showed that presence of autoantibodies was independently associated with stimulated C-peptide level (OR 2.3; 95%CI: 1.07–5.28, p=0.03).

Conclusions:

Autoimmune diabetes should be suspected in subjects with lower response of β- cell in glucagon stimulation test. If the C-peptide do not increase more than 1.6 after glucagon presence of autoanibodies is more probable.

 
  • References

  • 1 Hosszufalusi N, Vatay A, Rajczy K et al. Similar genetic features and different islet cell autoantibody pattern of latent autoimmune diabetes in adults (LADA) compared with adult-onset type 1 diabetes with rapid progression. Diabetes Care 2003; 26 (02) 452-457
  • 2 Gottsater A, Landin-Olsson M, Fernlund P et al. Beta-cell function in relation to islet cell antibodies during the first 3 yr after clinical diagnosis of diabetes in type II diabetic patients. Diabetes Care 1993; 16 (06) 902-910
  • 3 Knip M, Siljander H. Autoimmune mechanisms in type 1 diabetes. Autoimmun Rev 2008; 7 (07) 550-557
  • 4 Schafer SA, Machicao F, Fritsche A et al. New type 2 diabetes risk genes provide new insights in insulin secretion mechanisms. Diabetes Res Clin Pract 2011; 93 (Suppl. 01) S9-S24
  • 5 Tuomi T, Carlsson A, Li H et al. Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes 1999; 48 (01) 150-157
  • 6 Turner R, Stratton I, Horton V et al. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997; 350 (9087) 1288-1293
  • 7 Wroblewski M, Gottsater A, Lindgarde F et al. Gender, autoantibodies, and obesity in newly diagnosed diabetic patients aged 40–75 years. Diabetes Care 1998; 21 (02) 250-255
  • 8 Radtke MA, Midthjell K, Nilsen TI et al. Heterogeneity of patients with latent autoimmune diabetes in adults: linkage to autoimmunity is apparent only in those with perceived need for insulin treatment: results from the Nord-Trondelag Health (HUNT) study. Diabetes Care 2009; 32 (02) 245-250
  • 9 Katulanda P, Shine B, Katulanda GW et al. Diabetes mellitus among young adults in Sri Lanka – role of GAD antibodies in classification and treatment: the Sri Lanka Young Diabetes study. Diabetologia 2008; 51 (08) 1368-1374
  • 10 Pozzilli P, Di Mario U. Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention. Diabetes Care 2001; 24 (08) 1460-1467
  • 11 Lee SH, Kwon HS, Yoo SJ et al. Identifying latent autoimmune diabetes in adults in Korea: the role of C-peptide and metabolic syndrome. Diabetes Res Clin Pract 2009; 83 (02) e62-e65
  • 12 Hawa MI, Thivolet C, Mauricio D et al. Metabolic syndrome and autoimmune diabetes: action LADA 3. Diabetes Care 2009; 32 (01) 160-164
  • 13 Juneja R, Hirsch IB, Naik RG et al. Islet cell antibodies and glutamic acid decarboxylase antibodies, but not the clinical phenotype, help to identify type 1(1/2) diabetes in patients presenting with type 2 diabetes. Metabolism 2001; 50 (09) 1008-1013
  • 14 Tfayli H, Bacha F, Gungor N et al. Phenotypic type 2 diabetes in obese youth: insulin sensitivity and secretion in islet cell antibody-negative versus -positive patients. Diabetes 2009; 58 (03) 738-744
  • 15 Maruyama T, Shimada A, Kanatsuka A et al. Multicenter prevention trial of slowly progressive type 1 diabetes with small dose of insulin (the Tokyo study): preliminary report. Ann N Y Acad Sci 2003; 1005: 362-369
  • 16 Chaillous L, Bouhanick B, Kerlan V et al. Clinical and metabolic characteristics of patients with latent autoimmune diabetes in adults (LADA): absence of rapid beta-cell loss in patients with tight metabolic control. Diabetes Metab 2010; 36 (01) 64-70
  • 17 Desai M, Clark A. Autoimmune diabetes in adults: lessons from the UKPDS. Diabet Med 2008; 25 (Suppl. 02) 30-34
  • 18 Tiberti C, Giordano C, Locatelli M et al. Identification of tyrosine phosphatase 2(256–760) construct as a new, sensitive marker for the detection of islet autoimmunity in type 2 diabetic patients: the non-insulin requiring autoimmune diabetes (NIRAD) study 2. Diabetes 2008; 57 (05) 1276-1283
  • 19 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 (Suppl. 01) 62-69
  • 20 Chase HP, Cooper S, Osberg I et al. Elevated C-reactive protein levels in the development of type 1 diabetes. Diabetes 2004; 53 (10) 2569-2573
  • 21 Bonifacio E, Mollenhauer U, Buuck D et al. C-reactive protein concentration is not related to islet autoimmunity status in offspring of parents with type 1 diabetes. Clin Immunol 2005; 115 (02) 173-177
  • 22 Pietropaolo M, Barinas-Mitchell E, Kuller LH. The Heterogeneity of Diabetes. Diabetes 2007; 56 (05) 1189-1197
  • 23 Davis TM, Wright AD, Mehta ZM et al. Islet autoantibodies in clinically diagnosed type 2 diabetes: prevalence and relationship with metabolic control (UKPDS 70). Diabetologia 2005; 48 (04) 695-702
  • 24 Bottazzo GF, Bosi E, Cull CA et al. IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71). Diabetologia 2005; 48 (04) 703-708
  • 25 Huang G, Wang X, Li Z et al. Insulin autoantibody could help to screen latent autoimmune diabetes in adults in phenotypic type 2 diabetes mellitus in Chinese. Acta Diabetol 2010;
  • 26 Rogowicz A, Litwinowicz M, Piłaciński S et al. Does early insulin treatment decrease the risk of microangiopathy in non-obese adults with diabetes?. Arch Med Sci 2007; 2: 129-135
  • 27 Desai M, Cull CA, Horton VA et al. GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77. Diabetologia 2007; 50 (10) 2052-2060
  • 28 Thunander M, Thorgeirsson H, Torn C et al. beta-cell function and metabolic control in latent autoimmune diabetes in adults with early insulin versus conventional treatment: a 3-year follow-up. Eur J Endocrinol 2010; 164 (02) 239-245
  • 29 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329 (14) 977-986
  • 30 Epidemiology of Diabetes Interventions and Complications (EDIC) . Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999; 22 (01) 99-111
  • 31 Stratton IM, Adler AI, Neil HA et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321 (7258) 405-412
  • 32 Groop LC, Bottazzo GF, Doniach D. Islet cell antibodies identify latent type I diabetes in patients aged 35–75 years at diagnosis. Diabetes 1986; 35 (02) 237-241
  • 33 Gale EA. Latent autoimmune diabetes in adults: a guide for the perplexed. Diabetologia 2005; 48 (11) 2195-2199
  • 34 Naik RG, Palmer JP. Latent autoimmune diabetes in adults (LADA). Rev Endocr Metab Disord 2003; 4 (03) 233-241