Gastroesophageal reflux disease and progressive nephropathy after improving glycemic control in an adolescent with diabetic dwarfism.

W e describe the case of a 71-year-old man who was being followed as an outpatient for type 2 diabetes , hyperlipidemia, hypertension, and asthma. He was a past smoker with a BMI of 25.6 kg/m 2. Because he had only mild wheezing at night, he was not under medical treatment for asthma. As his level of HbA 1c remained between 6.6 and 6.8% under treatment with 2.5 mg gliben-clamide, 30 mg pioglitazone (an insulin-sensitizing drug) was added to his treatment. Several days later, he noticed that his wheezing had disappeared. The pulmonary function tests showed improvement of forced vital capacity from 2.33 to 3.02 l and forced expiratory volume in one second from 1.46 to 2.03 l, one month after the start of treatment with pioglitazone. No significant change was observed in the serum level of total IgE (76 vs. 66 IU/ml, reference interval Ͻ250 IU/ml). The level of HbA 1c (reference interval 4.3–5.8%) also decreased from 6.7 to 5.9% 3 months later. In this patient, pioglitazone seemed to be effective for both diabetes and asthma. Before treating this patient, we had treated another man with diabetes and asthma with pioglitazone. He had been on fenoterol hydrobromide by mouth and beclomethasone dipropionate by inhalation. Several days after he was started on 15 mg pioglitazone, he stopped wheezing and coughing. Pioglitazone was discontinued 6 months later because his level of HbA 1c had not decreased significantly, but his respiratory symptoms recurred. As this patient did not undergo pulmonary function tests, we had no objective evidence of the improvement of his asthma. Based on the findings obtained from these two patients with diabetes and asthma, we suppose that pioglitazone may ameliorate symptoms of asthma. Pio-glitazone is one of the thiazolidinedione compounds that have been used as anti-diabetic drugs (1). Recent studies have revealed that thiazolidinedione compounds also have various nonhypoglycemic effects , such as anti-inflamatory, anti-atherosclerotic, and anti-cancer effects, in cultured cells and experimental animal models (1,2). Although some of their effects are mediated through activation of the peroxisome proliferator–activated receptor -␥, an alternative mechanism has also been suggested (3). Thiazolidinedi-one compounds suppress the activation of macrophages and reduce nitric oxide and inflammatory cytokines, such as tumor necrosis factor-␣, interleukin-1␤, and interleukin-6 (4,5). In asthma, many mediators secreted from macrophages, mast cells, neutrophils, lymphocytes, and eosinophils are known to contribute to its pathogenesis. Pioglitazone may suppress the production of some of …