Impairment of exocrine as well as endocrine function of the pancreas has been reported in type 1 diabetes (1). Histologically, lymphocytic infiltration of the exocrine gland has been reported in about half of Japanese type 1 diabetic patients (2). Fibrosis and atrophy of the exocrine gland have also been reported.

On the other hand, the concept of autoimmune pancreatitis has been recently proposed (3). This new clinical entity is characterized by swelling of the pancreas with extensive fibrosis and lymphocyte infiltration in the exocrine pancreas (3,4,5). It has been suggested that carbonic anhidrase II, an antigen of the duct cells of the pancreas, or lactoferrin in the pancreatic acinus may be the candidates for the target antigen (6).We have reported the first case of association of autoimmune pancreatitis and type 1 diabetes as autoimmune exocrinopathy and endocrinopathy of the pancreas (7).

To test the hypothesis that autoimmunity against the exocrine pancreas is involved in the pathological process of type 1 diabetes, we investigated the presence of autoantibodies against carbonic anhidrase II and lactoferrin in type 1 diabetes.

Eighteen patients with type 1 diabetes (2 men and 16 women, aged 45.4 ±19.5 years, range 23–72) and 18 patients with type 2 diabetes (7 men and 11 women, aged 59.1 ± 10.9 years) as control subjects were recruited for the study after informed consent was obtained. Diabetes was diagnosed according to the new criteria of the American Diabetes Association. Diagnosis of type 1A (immune-mediated) diabetes was based on the presence of at least one of the two immunological markers: anti-GAD antibody (measured by radioimmunoassay [GAD Ab Cosmic; RSR, Cardif, U.K.]) or anti–IA-2 (tyrosine phosphatase–like protein) antibody (measured by radioimmunoassay [RSR]). Diagnosis of type 1B (idiopathic) diabetes was based on insulin deficiency and the absence of these immunological markers. Among 18 type 1 diabetic patients, 12 had type 1A diabetes and 6 had type 1B diabetes. One patient had chronic thyroiditis and one had Graves’ disease. There was no history of other autoimmune diseases in the other patients. No patient had a history of pancreatitis.

Serum levels of autoantibodies against carbonic anhidrase II (ACA) and against human lactoferrin (ALF) were measured using the solid-phase enzyme-linked immunosorbent assay, as previously described (8).

Of 18 patients with type 1 diabetes, ACA was detected in 9 patients and ALF was detected in 8 patients. A total of 12 (67%) patients tested positive for either of the two antibodies. In contrast, neither ACA nor ALF were detected in any patients with type 2 diabetes. The prevalences of both ACA and ALF in type 1 diabetic patients were significantly higher than those of type 2 diabetic patients (P < 0.01, χ2 test). Our results suggest the involvement of autoimmunity against the exocrine as well as endocrine pancreas in the pathogenesis of type 1 diabetes. These conditions could be referred to as autoimmune exocrinopathy and endocrinopathy of the pancreas.

In addition, it is noteworthy that either of these antibodies were detected in three of six type 1B diabetic patients. These observations suggest that ALF and ACA may be novel immunological markers for type 1 diabetes.

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Address correspondence to Takao Taniguchi, MD, PhD, Department of Internal Medicine, Ohtsu Red Cross Hospital, 1-1-35, Nagara, Ohtsu, Shiga, Japan.

2001