Korean Diabetes J.  2009 Apr;33(2):124-133. 10.4093/kdj.2009.33.2.124.

Chronic Complications in Adult Diabetic Patients with and without GAD Antibody

• Chung JO
• Cho DH
• Chung DJ
• Chung MY

• KMID: 2298069
• DOI: http://doi.org/10.4093/kdj.2009.33.2.124

Abstract

BACKGROUND
Although the majority of diabetes mellitus (DM) patients diagnosed as adults have non-autoimmune forms of the disease, islet autoimmunity is encountered in some patients initially thought to have type 2 DM. The phenotype of DM patients with glutamic acid decarboxylase (GAD) antibodies is different from that of patients with GAD antibody-negative type 2 DM, with features such as relative leanness and hyperglycemia which may influence the development of complications. We sought to compare the prevalence of chronic complications in patients with and without the GAD antibody. METHODS: We recruited 427 patients (M: 218, F: 209) that were clinically diagnosed with type 2 DM after the age of 35 years. We measured GAD antibody and assessed the factors associated with chronic microvascular and macrovascular complications. RESULTS: Of these patients, 26 were GAD antibody-positive. The patients with GAD antibody had lower systolic blood pressure, higher high-density lipoprotein cholesterol value, and lower level of fasting and stimulated C-peptide than patients without GAD antibody (P < 0.05). Also, the patients with GAD antibody had lower prevalence of retinopathy compared with the patients without GAD antibody (19.2 vs. 47.9%; P < 0.05). The prevalence of nephropathy, peripheral neuropathy and cardiovascular autonomic neuropathy did not differ between the groups. In addition, the prevalence of coronary heart disease, cerebrovascular disease and peripheral arterial disease did not differ between the two groups. CONCLUSION: This study suggests that diabetic patients with GAD antibody have a lower risk for the development of retinopathy compared with patients without GAD antibody.

Keyword

Diabetes Complications; Diabetes Mellitus; Glutamate decarboxylase

MeSH Terms

Adult
Antibodies
Autoimmunity
C-Peptide
Cholesterol
Coronary Disease
Diabetes Complications
Diabetes Mellitus
Fasting
Glutamate Decarboxylase
Humans
Hyperglycemia
Hypertension
Lipoproteins
Peripheral Arterial Disease
Peripheral Nervous System Diseases
Phenotype
Prevalence
Thinness
Antibodies
C-Peptide
Cholesterol
Glutamate Decarboxylase
Lipoproteins

Reference

1. Landin-Olsson M, Palmer JP, Lernmark A, Blom L, Sundkvist G, Nyström L, Dahlquist G. Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children. Diabetologia. 1992. 35:1068–1073.

2. Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes. 1993. 42:359–362.

3. UK Prospective Diabetes Study Group. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. Lancet. 1997. 350:1288–1293.

4. Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, Lang DA. Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med. 1994. 11:299–303.

5. Skyler JS. Diabetic complications. The importance of glucose control. Endocrinol Metab Clin North Am. 1996. 25:243–254.

6. Wagenknecht LE, D'Agostino RB Jr, Haffner SM, Savage PJ, Rewers M. Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study. Diabetes Care. 1998. 21:1812–1818.

7. Birkeland KI, Kilhovd B, Thorsby P, Torjesen PA, Ganss R, Vaaler S, Hanssen KF. Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity, beta-cell function and cardiovascular risk profile. Diabet Med. 2003. 20:37–45.

8. Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Cardiovascular risk factors clustering with endogenous hyperinsulinaemia predict death from coronary heart disease in patients with Type II diabetes. Diabetologia. 2000. 43:148–155.

9. Tuomi T, Carlsson A, Li H, Isomaa B, Miettinen A, Nilsson A, Nissén M, Ehrnström BO, Forsén B, Snickars B, Lahti K, Forsblom C, Saloranta C, Taskinen MR, Groop LC. Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes. 1999. 48:150–157.

10. 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. 53:3193–3200.

11. Arikan E, Sabuncu T, Ozer EM, Hatemi H. The clinical characteristics of latent autoimmune diabetes in adults and its relation with chronic complications in metabolically poor controlled Turkish patients with Type 2 diabetes mellitus. J Diabetes Complications. 2005. 19:254–258.

12. Balme M, McAllister I, Davis WA, Davis TM. Retinopathy in latent autoimmune diabetes of adults: the Fremantle Diabetes Study. Diabet Med. 2002. 19:602–605.

13. Myhill P, Davis WA, Bruce DG, Mackay IR, Zimmet P, Davis TM. Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study. Diabet Med. 2008. 25:1245–1250.

14. Kim CS, Park JA, Cho MH, Park JS, Nam JY, Kim DM, Ahn CW, Cha BS, Lim SK, Kim KR, Lee HC. The frequency of anti-GAD antibody in non-obese, adult-onset type 2 diabetes in Korea and clinical and biological characteristics according to anti-GAD antibody. J Korean Diabetes Assoc. 2004. 28:66–74.

15. Oh JH, Yoon JS, Won KC, Lee HW. Antibodies to GAD and ICA in type 2 DM with secondary failure of oral hypoglycemic therapy. J Korean Diabetes Assoc. 2007. 31:402–409.

16. Leslie RD, Atkinson MA, Notkins AL. Autoantigens IA-2 and GAD in Type I (insulin-dependent) diabetes. Diabetologia. 1999. 42:3–14.

17. Kim KA, Ahn KJ, Chung JH, Min YK, Lee MK, Oh PS, Jin DK, Kim BT, Park HJ, Kim KW, Lee MS. Combined measurements of anti - ICA512 and anti - GAD antibodies in insulin - dependent diabetes mellitus and slowly progressive insulin - dependent diabetes mellitus in Korea. J Korean Diabetes Assoc. 1998. 22:482–491.

18. Takino H, Yamasaki H, Abiru N, Sera Y, Abe T, Kawasaki E, Yamaguchi Y, Eguchi K, Kanazawa Y, Nagataki S. Antibodies to GAD in Japanese patients classified as Type 2 diabetes at diagnosis. High titre of GAD Ab is a predictive marker for early insulin treatment--report of west Japan (Kyushu, Yamaguchi, Osaka) study for GAD Ab(+) diabetes. Diabet Med. 2002. 19:730–734.

19. Rattarasarn C, Aguilar Diosdado M, Soonthornpun S. Glutamic acid decarboxylase antibodies in non-insulin-dependent diabetes patients with secondary sulfonylurea failure in Thailand. Diabetes Res Clin Pract. 1997. 37:193–197.

20. Littorin B, Sundkvist G, Hagopian W, Landin-Olsson M, Lernmark A, Ostman J, Arnqvist HJ, Blohmé G, Bolinder J, Eriksson JW, Lithner F, Scherstén B, Wibell L. Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes. Diabetes Care. 1999. 22:409–412.

21. Niskanen LK, Tuomi T, Karjalainen J, Groop LC, Uusitupa MI. GAD antibodies in NIDDM. Ten-year follow-up from the diagnosis. Diabetes Care. 1995. 18:1557–1565.

22. Song TH, Choi BR, Tak SM, Kang JW, Kim CE, Moon FC, Woo JT, Kim EJ. A retrospetive study on body weight of diabetes in Korea. J Korean Diabetes Assoc. 1990. 14:229–234.

23. Owen KR, Stride A, Ellard S, Hattersley AT. Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes. Diabetes Care. 2003. 26:2088–2093.

24. Baum P, Hermann W, Verlohren HJ, Wagner A, Lohmann T, Grahmann F. Diabetic neuropathy in patients with "latent autoimmune diabetes of the adults" (LADA) compared with patients with type 1 and type 2 diabetes. J Neurol. 2003. 250:682–687.

25. Vinik AI, Leichter SB, Pittenger GL, Stansberry KB, Holland MT, Powers AC, Suwanwalaikorn S. Phospholipid and glutamic acid decarboxylase autoantibodies in diabetic neuropathy. Diabetes Care. 1995. 18:1225–1232.

26. Moon SJ, Lee CH, Moon JS, Moon HJ, Lee JE, Chun KA, Yoon JS, Cho IH, Won KC, Lee HW. Prevalence of diabetic retinopathy in diabetics who are positive for GAD autoantibody. J Korean Diabetes Assoc. 2007. 31:429–434.

27. Zimmet P. Addressing the insulin resistance syndrome: a role for the thiazolidinediones. Trends Cardiovasc Med. 2002. 12:354–362.

28. Alexander CM, Landsman PB, Teutsch SM, Haffner SM. Third National Health and Nutrition Examination Survey (NHANES III); National Cholesterol Education Program (NCEP): NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes. 2003. 52:1210–1214.