Do Latent Autoimmune Diabetes of the Adult (LADA) Patients Require Insulin at Diagnosis?: Response to Pozzilli and Di Mario

In the August 2001 issue of Diabetes Care, Paolo Pozzilli and Umberto Di Mario (1) present their current opinion about the definition, characterization, and potential prevention of latent autoimmune diabetes in adults (LADA). We read their article with great interest, especially as it concerns different treatments of patients with LADA. Because 10–15% of adult diabetic patients may have autoimmune diabetes, management in this group seems to be a very important question. Yet, we do not fully concur with Pozzilli and Di Mario’s conclusion that LADA does not require insulin at diagnosis. In our experience, treatment with insulin at the onset of the disease (when the autoimmune background is proven) is of special clinical benefit (2).

There is strong evidence that LADA is an autoimmune form of diabetes. Shimada et al. (3) have reported their findings of T-cell insulitis in an anti–GAD- positive 65-year-old patient with diabetes and residual β-cell function. The latter is assumed to be similar to type 1 diabetes, with genetic susceptibility and presence of autoimmune markers.

In NOD mice and BB rat models, subcutaneous or oral administration of insulin can prevent the onset of diabetes (4,5). Such insulin administration is thought to provide a form of β-cell “rest,” protecting them from destruction. Insulin is also considered to be an immunomodulator. It increases production of Th² profile cytokines in peripheral blood in subjects at high risk and in newly diagnosed type 1 diabetic patients (6).

A 1996 report suggests that insulin therapy may also help in preventing C-peptide secretion in LADA patients, and that such patients appear to lose expression of islet cell antibodies faster than patients treated with oral hypoglycemic drugs (7). Furthermore, treatment of LADA patients with hypoglycemic drugs was not satisfactory, and they showed insulin dependency quicker than patients with type 2 diabetes (8,9). Finally, some anti-GAD65 antibodies recognize patients with risk for insulin requirement (10). Earlier treatment of diabetes with insulin may improve their quality of life, thus potentially saving β-cell function and perhaps lessening the risk of long-term microvascular complications. Because the use of insulin as a preventive agent is still under investigation (11), the discussion about management of LADA patients still remains open.