10 April 2014 : Original article
Alogliptin improves steroid-induced hyperglycemia in treatment-naïve Japanese patients with chronic kidney disease by decrease of plasma glucagon levels
Naro OhashiABCDEFG, Naoko TsujiB, Yoshitaka NaitoB, Takamasa IwakuraB, Shinsuke IsobeB, Masafumi OnoB, Tomoyuki FujikuraB, Takayuki TsujiB, Yukitoshi SakaoB, Hideo YasudaDE, Akihiko KatoDE, Yoshihide FujigakiACDEGDOI: 10.12659/MSM.889872
Med Sci Monit 2014; 20:587-593
Abstract
BACKGROUND: Chronic kidney disease (CKD) is a risk factor for end-stage renal failure and cardiovascular disease, and a strategy to counteract CKD must be established. CKD caused by immunological abnormalities is treated by steroids, frequently resulting in steroid diabetes. Although insulin is the most effective drug against steroid diabetes, administering it to patients can be difficult. Dipeptidyl peptidase-4 (DPP-4) inhibitors were developed for diabetes mellitus with a new mechanism of action. However, their efficacies and mechanisms of action for steroid diabetes are unclear.
MATERIAL AND METHODS: We studied 11 CKD patients treated with steroids admitted to our hospital (3 men and 8 women; age, 66.0±15.9 years). DPP-4 inhibitor alogliptin was administered for steroid diabetes. Levels of markers related to glucose metabolism were measured before alogliptin treatment and after alogliptin treatment, before the prednisolone dose was reduced.
RESULTS: Alogliptin treatment significantly increased plasma glucagon-like peptide-1 (GLP-1) levels from 1.16±1.71 pmol/L to 4.48±1.53 pmol/L and significantly reduced levels of plasma glucose recorded 2 h after lunch and hemoglobin A1c (HbA1c). No significant differences were seen in insulin secretory ability of homeostasis model assessment (HOMA) (HOMA-β) and insulin resistance index of HOMA (HOMA-R) before and after alogliptin treatment. In contrast, alogliptin treatment significantly decreased plasma glucagon levels, from 116.1±38.7 pg/mL to 89.6±17.3 pg/mL. Moreover, there were significant correlations among HbA1c, GLP-1, and glucagon levels.
CONCLUSIONS: Alogliptin improves steroid-induced hyperglycemia by decrease of glucagon levels through an increase in plasma GLP-1 levels.
Keywords: Body Mass Index, Asian Continental Ancestry Group, Glucagon - blood, Glucagon-Like Peptide 1 - metabolism, Hemoglobin A, Glycosylated - metabolism, Hyperglycemia - drug therapy, Japan, Kidney Function Tests, Piperidines - therapeutic use, Regression Analysis, Renal Insufficiency, Chronic - physiopathology, Steroids - adverse effects, Uracil - therapeutic use, Vital Signs - drug effects
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