J Korean Diabetes Assoc.  2007 Sep;31(5):402-409.

Antibodies to GAD and ICA in Type 2 DM with Secondary Failure of Oral Hypoglycemic Therapy

• Oh JH
• Yoon JS
• Won KC
• Lee HW

Abstract

BACKGROUND: Secondary failure of oral hypoglycemic agents is defined as that blood glucose is no longer controlled with sulfonylurea after a proven period of good glycemic control. There are many causes of secondary failure, including that drug problem, acute illnesses, inappropriate drug dosages, oxidative stress & glucose toxicity of beta-cell, etc. And many studies have suggested role of immunologic process such as islet cell antibody (ICA) and/or glutamic acid decarboxylase antibody (GADA) for the causes of secondary failure. So we evaluated the prevalence of ICA & GADA in type 2 diabetes with secondary failure of oral hypoglycemic agents and the pathogenesis of the secondary failure.
METHODS
We studied 267 patients with type 2 diabetes. We regarded 84 patients who could not control HbA1c less than 8% after good glycemic control for at least 1 year as secondary failure group (group 1) and regarded the other 183 patients as group 2. We measured GADA in both group, and measured the prevalence of GADA and ICA in secondary failure group who were especially divided into obese group and nonobese group according to BMI and were divided into insulin deficiency group and noninsulin deficiency group according to fasting C-peptide level.
RESULTS
The prevalence of GADA in all subjects was 4.1%, which was 9.5% in group 1 and 1.6% in group 2 (P < 0.05). Among 35 patients of the group 1 who could be checked ICA, the prevalence of GADA & ICA were 33% & 25% in insulin deficiency group and 4.3% & 0% in non-insulin deficiency group, respectively (P < 0.05). The prevalence of GADA & ICA were none in obese group and 33.3% & 20% in nonobese group, respectively (P < 0.05). The prevalence of GADA & ICA were 36.4% & 27.3% in nonobese and insulin deficiency, 4.2% & 0% in obese and non-insulin deficiency.
CONCLUSION
We suggest that autoimmune mechanism is associated with increased risk for secondary failure of oral hypoglycemic agents in type 2 diabetes, so the measurement of GADA and ICA could help to predict the potential risk and insulin treatment.

Keyword

GADA; ICA; Oral hypoglycemic therapy; Secondary failure

MeSH Terms

Antibodies*
Blood Glucose
C-Peptide
Fasting
Glucose
Glutamate Decarboxylase
Humans
Hypoglycemic Agents
Insulin
Islets of Langerhans
Oxidative Stress
Prevalence
Antibodies
Blood Glucose
C-Peptide
Glucose
Glutamate Decarboxylase
Hypoglycemic Agents
Insulin

Figure

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  Fig. 1 Causes of secondary failure.

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  Fig. 2 The prevalence of GADA in group 1 (8/84, 9.5%) and in group 2 (3/183, 1.6%). *P < 0.05

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  Fig. 3 The prevalence of GADA and ICA in secondary failure group. According to insulin deficiency, the prevalence of GADA (A) & ICA (B, in 35 patients of the group 1) were significantly different. According to BMI, the prevalence of GADA (C) & ICA (D, in 35 patients of the group 1) were significantly different. *P < 0.05

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  Fig. 4 The prevalence of GADA(A) and ICA(B) between nonobese & insulin deficient group and obese & noninsulin deficient group were significantly different. *P < 0.05

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