Elsevier

Endocrine Practice

Volume 18, Issue 4, July–August 2012, Pages e65-e68
Endocrine Practice

Case Report
Sitagliptin in Glutamic Acid Decarboxylase Antibody-Positive Diabetes Mellitus

https://doi.org/10.4158/EP11340.CRGet rights and content

ABSTRACT

Objective

To describe a case illustrating the use of sitagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4), in anti-glutamic acid decarboxylase antibody-positive diabetes mellitus in association with a rare ataxic variant of stiff person syndrome.

Methods

We present our experience with use of the DPP-4 inhibitor sitagliptin for management of autoimmune diabetes in a elderly woman and highlight the association of diabetes with other autoimmune conditions.

Results

A 68-year-old Japanese woman presented with poorly controlled “type 2” diabetes mellitus, cerebral palsy, cerebellar ataxia, and hypothyroidism. She complained of stiffness and spasms, which had resulted in multiple falls and immobility. Antidiabetic medications included gliclazide, rosiglitazone, and acarbose; various insulins had been tried but discontinued because they worsened her stiffness and spasms. Her hemoglobin A1c values remained above 9% despite maximal doses of the aforementioned orally administered hypoglycemic agents. After sitagliptin therapy was initiated, her hemoglobin A1c level decreased from 9.3% (78 mmol/mol) to 7.3% (56 mmol/mol) in 5 months. Investigations confirmed the presence of an ataxic variant of stiff person syndrome. On repeated testing 18 months later, her anti-glutamic acid decarboxylase antibody levels had declined by more than 85%.

Conclusion

Apart from the well-known mechanism of an increase in glucagonlike peptide-1, sitagliptin may exert its glucose-lowering effect by other mechanisms in patients with autoimmune diabetes. Further studies should be undertaken to address the effectiveness of DPP-4 inhibitors in non-type 2 diabetes. (Endocr Pract. 2012;18: e65-e68)

Section snippets

INTRODUCTION

Dipeptidyl-peptidase-4 (DPP-4) inhibitors lower the blood glucose level in patients with type 2 diabetes mellitus by inhibiting the degradation of endogenous glucagonlike peptide-1 (GLP-1) and thus enhancing GLP-1 action. DPP-4 has 62 endogenous substrates and is present in lymphocytes as CD26 (1). The effect of DPP-4 inhibition on the immune system has not been well studied. We describe the case of a woman with glutamic acid decarboxylase (GAD) antibody-positive diabetes mellitus, autoimmune

CASE REPORT

A 68-year-old Japanese woman presented in 2006 with poorly controlled “type 2” diabetes of 10 years’ duration. Her medical history included cerebral palsy and primary hypothyroidism.

The patient’s neurologic symptoms were stable until 1998, after which her mobility gradually worsened, accompanied by increasing cerebellar ataxia. Her glycemic control progressively deteriorated during a period of 2 years from an A1C level of less than 7.5% (58 mmol/mol) before 2000 to greater than 10% (86

DISCUSSION

This case suggests a possible role for sitagliptin in improving glycemic control in patients with GAD antibody-positive diabetes. In addition to the effects of sitagliptin on insulin secretion, we explore other mechanisms by which sitagliptin may improve glycemia.

DPP-4 is present in the immune system as CD26 on lymphocytes. It is an activation marker for T lymphocytes, B lymphocytes, and natural killer cells (1). Its immunoregulatory functions include antigen recall, immunoglobulin synthesis,

CONCLUSION

This case raises the potential for use of DPP-4 inhibitors in patients with GAD antibody-positive or autoimmune diabetes. We acknowledge that our experience is based on a single case, and further studies are needed to explore this potentially useful therapeutic role of DPP-4 inhibitors.

DISCLOSURE

The authors have no multiplicity of interest to disclose.

ACKNOWLEDGMENT

We thank Dr Angela Vincent, Professor of Neuroimmunology, University of Oxford, for her helpful advice on the immunologic aspects of this case.

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