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

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.

• Authors: Naro Ohashi, Naoko Tsuji, Yoshitaka Naito, Takamasa Iwakura, Shinsuke Isobe, Masafumi Ono, Tomoyuki Fujikura, Takayuki Tsuji, Yukitoshi Sakao, Hideo Yasuda, Akihiko Kato, Yoshihide Fujigaki
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 20 Pg. 587-93 (Apr 10 2014) ISSN: 1643-3750 [Electronic] United States
• PMID: 24717767 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Glycated Hemoglobin A
• Piperidines
• Steroids
• Uracil
• Glucagon-Like Peptide 1
• Glucagon
• alogliptin

Topics

• Aged
• Asian People
• Body Mass Index
• Female
• Glucagon (blood)
• Glucagon-Like Peptide 1 (metabolism)
• Glycated Hemoglobin (metabolism)
• Humans
• Hyperglycemia (chemically induced, drug therapy)
• Japan
• Kidney Function Tests
• Male
• Piperidines (pharmacology, therapeutic use)
• Regression Analysis
• Renal Insufficiency, Chronic (blood, drug therapy, physiopathology)
• Steroids (adverse effects)
• Uracil (analogs & derivatives, pharmacology, therapeutic use)
• Vital Signs (drug effects)