Therapeutic Effect of Rosiglitazone on Chronic Obstructive Pulmonary Disease with Diabetes Mellitus
|School||Dalian Medical University|
|Course||Pathology and Pathophysiology|
|Keywords||COPD diabetes mellitus rosiglitazone antiinflammation glycemic control|
Backgrounds and purpose: Chronic obstructive pulmonary diseases (COPD)is a group of diseases characterized by progressive limitation of expiratory airflow. Inflammation, Oxidative Stress and imbalance between proteinases and antiproteinases were main pathogenesis of COPD. Diabetes mellitus is a common chronic metabolic disease. Persistent hyperglycemia can cause metabolic abnormalities, dysfunction and structural change of some tissues. Lung was one of targeted organs injured by microvascular lesion of diabetes mellitus, manifestation of pulmonary dysfunction included restrictive, obstructive and mixed hypoventilation and diffuse impairment. Proinflammatory factors played important roles in the course of COPD and type 2 diabetes mellitus. Peroxisome proliferators - activated receptorγ(PPARγ) are ligand-activated transcription factors belonging to the nuclear hormone receptor family that regulates immune and inflammatory responses negatively. Rosiglitazone is an insulin-sensitizing agent widely in type 2 diabetes mellitus that exerts its biological effects in part via PPARγ。Our previous experiments showed that rosiglitazone had preventive and therapeutic effects on rat COPD modeled with smoking and LPS. Here, we investigated the therapeutic effect of rosiglitazone on COPD with diabetes mellitus to determine whether rosiglitazone may used to treat patients with COPD or both and safe.Participants and methods:60 patients suffered from COPD with diabetes mellitus, male (31 cases), female in 29 cases, were researched in Dalian friendship hospital December 2008 - June 2010. They were randomly divided into two groups, each has 30 patients. In conventional therapy group patients were administered with insulin. In rosiglitazone therapy group patients without ketonemia were administered orally with rosiglitazone, 8mg/ once/daily before breakfast for 7 days, patients with ketonemia were treated with combined rosiglitazone and insulin. All of patients were treated with same drugs to control acute exacerbation of COPD, including anti-infectious quinolone combined with half synthetic penicillin, oral expectorant ambroxol hydrochloride, bronchodilators salbutamol sulphate aerosol with ipratropine and theophylline. Indexes measured included①number of white blood cells and platelets, percent of neutrophils and content of hemoglobin;②PaO2 and PaCO;③erythrocyte sedimentation rate (ESR);④blood glucose levels;⑤serum urea nitrogen and creatinine. Mean and standard deviation of above indexes were calculated and analyzed using SPSS13.0 (Matching Student t test); P < 0.05 was considered to be significant statistically.Results:①A fter treated with combined insulin or rosiglitazone with antibiotics, expectorants and bronchodilators platelets number and PaO2 of patients did not changed significantly.②The hemoglobin content, serum urea nitrogen and creatinine of patients in both groups was in normal range before and after treatment.③In rosiglitazone therapy group the number of white blood cells and percent of neutrophils of untreated patients was 14.1±3.9×109/L and 82.6±9.5%,respectively. that indexes of patients treated with rosiglitazone was 6.1±1.6×109/L and 66.3±7.7% respectively(p<0.01). In conventional therapy group the number of white blood cells and percent of neutrophils of untreated patients was 12.3±5.0×109/L and 79.8±10.7%,respectively. that indexes of patients treated with insulin were 5.7±1.5×109/L and 57.7±7.66% respectively(p<0.01).④I n rosiglitazone therapy group PaCO2 of untreated patients was 52.8±20.8 mmHg,that of patients treated with rosiglitazone was 40.4±5.7 mmHg ( p<0.01 )。In conventional therapy group PaCO2 of untreated patients was 47.9±19.6 mmHg,that of patients treated with insulin was 36.1±4.5 mmHg(p<0.01).⑤In rosiglitazone therapy group ESR of untreated patients was 28.1±14.9 mm/h,that of patients treated with rosiglitazone was 19.4±6.4 mm/h(p<0.01). In conventional therapy group ESR of untreated patients was 27.9±15 mm/h,that of patients treated with insulin was 18.1±6.8 mm/h(p<0.01).⑥In rosiglitazone therapy group blood glucose levels of untreated patients was 12.7±4.6 mmol/L,that of patients treated with rosiglitazone was 6.3±1.2 mmol/L(p<0.01). In conventional therapy group blood glucose levels of untreated patients was 12.2±5.0 mmol/L,that of patients treated with insulin was 6.1±1.1 mmol/L(p<0.01)。The differences in above indexes between both groups were not significant statistically(p>0.05). Conclusions: In patients without ketonemia rosiglitazone only causes a significant decrease for blood glucose levels, the difference between both groups was not significant statistically. No renal dysfunction was observed. PPARγagonist rosiglitazone may be used to treated COPD with diabetes mellitus and beneficial to improve insulin sensitivity and glycemic control and antiinflammation without severe toxicity.