Recent studies have shown that bilirubin is negatively associated with hemoglobin A1c (HbA1c) in the general population. The association between bilirubin and HbA1c in serum of diabetes patients has not yet been studied. The aim of the present study was to evaluate the association between total bilirubin and HbA1c in Korean patients with type 2 diabetes. A total of 690 of the 1,275 type 2 diabetes patients registered with the public health centers in Seo-gu, Gwangju and Gokseong-gun, Jeollanam-do participated in this study. Following an overnight fast, venous blood and urine samples were collected and analyzed. The mean HbA1c values differed significantly according to total bilirubin (< or = 0.4 mg/dL, 7.6%; 0.5 mg/dL, 7.3%; 0.6-0.7 mg/dL, 7.2%; and > or = 0.8 mg/dL, 7.1%; P for trend = 0.016) after we adjusted for other confounding factors. When the odds ratio (OR) was adjusted for other confounding factors, there was a significant association between total bilirubin and HbA1c (OR, 0.4 [95% confidence interval, 0.2-0.8] for total bilirubin > or = 0.8 mg/dL versus < or = 0.4 mg/dL. In conclusion, total bilirubin concentrations in serum are negatively associated with HbA1c levels after adjustment for sex, age, and other confounding factors in type 2 diabetes patients.
Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Bilirubin/*analysis/blood/urine ; Diabetes Mellitus, Type 2/*blood/diagnosis ; Female ; Hemoglobin A, Glycosylated/*analysis/urine ; Humans ; Male ; Middle Aged ; Odds Ratio ; Republic of Korea ; Risk Factors

OBJECTIVETo assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.

METHODSA total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group): four groups were treated with rhG-CSFa at 500, 100, 10, 1 µg/kg, respectively, and one group was treated with vehicle only to serve as the control. The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks. During the course of the chronic toxicity study, the physical status, body weight, and food consumption were monitored. Half of the rats in each group (n = 10) were sacrificed after the last rhG-CSFa administration, and the other half were sacrificed at five weeks after the last rhG-CSFa administration. Urinalyses, blood biochemistry, hematological analysis, histopathological examination, and immunological tests were performed for each of the rats.

RESULTSThe hematological analyses revealed that the mean white blood cells count, neutrophils count, and neutrophils percentage were increased in male rats at the dose of 10 µg/kg or higher, and these were related with the biological activity of rhG-CSFa. Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 µg/kg, a dosage of 200 folds higher than the normal clinical dosage), but these abnormalities were recovered within 5-week recovery period. No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.

CONCLUSIONNo significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

Animals ; Bilirubin ; urine ; Blood Chemical Analysis ; Dose-Response Relationship, Drug ; Female ; Granulocyte Colony-Stimulating Factor ; genetics ; toxicity ; Humans ; Lung ; cytology ; drug effects ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; Spleen ; cytology ; drug effects ; Trachea ; cytology ; drug effects