Alogliptin improves steroid-induced hyperglycemia in treatment-naïve Japanese patients with chronic kidney disease by decrease of plasma glucagon levels.
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.


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.
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Naro
N
Ohashi
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Naoko
N
Tsuji
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yoshitaka
Y
Naito
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takamasa
T
Iwakura
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Shinsuke
S
Isobe
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Masafumi
M
Ono
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Tomoyuki
T
Fujikura
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takayuki
T
Tsuji
Department of Blood Purification Unit, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yukitoshi
Y
Sakao
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hideo
H
Yasuda
Department of Blood Purification Unit, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Akihiko
A
Kato
Department of Internal Medicine 1, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yoshihide
Y
Fujigaki
D000368:Aged; D044466:Asian People; D015992:Body Mass Index; D005260:Female; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced* / Q000188:drug therapy*; D007564:Japan; D007677:Kidney Function Tests; D008297:Male; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013256:Steroids / Q000009:adverse effects*; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D055986:Vital Signs / Q000187:drug effects
D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D010880:Piperidines; D013256:Steroids; D014498:Uracil; C520853:alogliptin