Table 2. Predictors of steroid-induced DM (multivariable analysis) Parameters Age* (yr) Sex, Male Smoking Pack-years Hyperlipidemia Idiopathic interstitial pneumonias Endobronchial tuberculosis *(year X + 1 vs year X). Odds ratio 1.05 1.70 1.36 1.02 2.12 1.19 0.38 95% confidence interval (1.02-1.09) (0.48-5.99) (0.29-6.32) (0.99-1.05) (0.47-9.47) (0.36-3.86) (0.06-2.31) P value 0.006 0.41 0.70 0.22 0.33 0.78 0.30 bronchial tuberculosis (60 patients), sarcoidosis (43 patients), and hypersensitivity pneumonitis (three patients). The median random glucose before initiating glucocorticoid in the 231 patients was 101 mg/dL (range 59–198 mg/dL). The median cumulative prednisolone-equivalent dose of glucocor- ticoid was 4,965 mg (range 560-32,585 mg), and the median du- ration of steroid treatment was 193 days (range 28-1,869 days). S-DM was diagnosed in 34 (14.7%) out of 231 patients. Risk factors of steroid-induced diabetes The patients who developed S-DM were older than the patients who did not (65 vs 53 yr, P < 0.001). In addition, idiopathic in- terstitial pneumonitis was more common (79.4% vs 49.7%, P = 0.001), and endobronchial tuberculosis was less common (5.9% vs 29.4%, P = 0.004) among patients with S-DM than among those without S-DM. However, neither the cumulative dose nor the duration of glucocorticoid use was associated with the develop- ment of S-DM (Table 1). Multiple logistic regression analysis revealed that only older age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.09) was an independent risk factor for developing S-DM (Table 2). Evolution of steroid-induced diabetes The median time of onset of S-DM was 91.5 days (range 15-1,733 days); 18 patients (52.9%) were diagnosed in the first 3 months, and five patients (14.5%) after 1 yr. Among the 23 patients fol- lowed for longer than 6 months after the diagnosis of S-DM, 10 were treated with oral hypoglycemic drugs and five with insu- lin. The other eight patients were observed without treatment. Treatment for S-SM could be stopped after a median of 202 days (range 47-1,621 days) in seven of the 15 patients in whom hy- poglycemic agents and insulin were initiated. DISCUSSION Glucocorticoids can cause hyperglycemia via insulin resistance, which augments hepatic gluconeogenesis and lowers glucose uptake by peripheral tissues such as muscle cells and adipocytes (2, 6). For these reasons, it is not uncommon to observe abnor- mal glucose tolerance among patients receiving steroid thera- 266 http://jkms.org Kim SY, et al. • Steroid-induced Diabetes py. In the present study of 231 patients with respiratory diseases who received glucocorticoid, 34 (14.7%) of the patients experi- enced S-DM. Given that the incidence of S-DM in other condi- tions requiring glucocorticoids, such as connective tissue dis- eases, was between 0.4% and 54% (7-11), the proportion of pa- tients with respiratory disease treated with steroid who devel- oped S-DM in our study is comparable. The wide variability may reflect different study populations, doses of glucocorticoid, du- ration of follow-up, and different diagnostic criteria for S-DM. Proposed risk factors for S-DM included old age, high BMI, impaired glucose tolerance before therapy, cumulative dose, and long duration of steroid therapy. However, these results were not always consistent across studies (10-13). In our series of 231 patients treated with steroid for respiratory diseases, only old age was an independent risk factor for S-DM. Glucose tolerance declines progressively with age, resulting in a high incidence of type 2 diabetes and impaired glucose tol- erance in the old population (14, 15). According to the Korean National Health and Nutrition Examination Survey (16), 45% of Koreans 65 yr and older meet the diagnostic criteria for type 2 diabetes or impaired glucose tolerance. With aging, beta-cell function declines, and basal insulin secretion level decreases (17). In addition, the interaction of many factors associated with aging likely contributes to the altered glucose tolerance. These factors include obesity, decreased physical activity, medications, and coexisting illness (18). Considering the vulnerability of the aged population to glucose intolerance, the association of S-DM and age in our study can be understood. To appreciate our results correctly, we should consider the limitations of this study. The effects of glucocorticoid on glu- cose metabolism are greater in the postprandial state than when fasting (10, 11, 19). In our study, however, we monitored fasting blood glucose rather than the postprandial plasma glucose lev- el. In this context, our study could underestimate the incidence of S-DM. In conclusion, S-DM is frequent among patients with respi- ratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of steroid-induced DM, especially among old patients. REFERENCES 1. De Bosscher K, Vanden Berghe W, Haegeman G. Mechanisms of anti- inflammatory action and of immunosuppression by glucocorticoids: negative interference of activated glucocorticoid receptor with transcrip- tion factors. J Neuroimmunol 2000; 109: 16-22. 2. Clore JN, Thurby-Hay L.Glucocorticoid-induced hyperglycemia. Endocr Pract 2009; 15: 469-74. 3. The DECODE study group on behalf of the Europe an Diabetes Epide- miology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria. Lancet 1999; 354: 617-21. DOI: 10.3346/jkms.2011.26.2.264