Elevated serum levels of interleukin-18 in patients with overt diabetic nephropathy: effects of miglitol.
BACKGROUND
Interleukin-18 (IL-18), a pro-inflammatory cytokine, is a predictor of cardiovascular and renal disease in diabetic patients. Postprandial hyperglycemia is one of the important factors contributing to an increase in the circulating pro-inflammatory cytokine levels. This study investigated the effect of miglitol, an α-glucosidase inhibitor, on postprandial hyperglycemia and IL-18 levels in diabetic patients with nephropathy.


METHODS
Fifteen Japanese diabetic patients with persistent proteinuria and preserved renal function were recruited. The patients received 50 mg miglitol thrice daily after the baseline examinations and were followed up for 12 weeks. A meal tolerance test was performed on eight patients at baseline and week 12. The fasting miglitol concentration was measured in seven patients just before the meal tolerance test.


RESULTS
There were no changes in the body weight, blood pressure, liver and renal function, and proteinuria from baseline to week 12. However, the levels of glycated hemoglobin and interleukin 18 significantly decreased from baseline to week 12. During the meal tolerance test, plasma glucose was significantly decreased 60 min after treatment with miglitol, whereas the serum concentration of insulin was not changed. Fasting and postprandial levels of IL-18 were significantly decreased from baseline to week 12. Serum miglitol concentrations showed a significantly negative correlation with eGFR (r = -0.82, p = 0.02). However, the serum miglitol concentrations did not changed during the course of this study.


CONCLUSIONS
Miglitol improved postprandial hyperglycemia and reduced serum IL-18 levels in patients with stage 3 diabetic nephropathy. Miglitol may therefore prevent atherosclerotic diseases and diabetic micro-vascular complications through decreasing glucose swings and/or the circulating IL-18 level.
Uzu
Takashi
T
Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. takuzu@belle.shiga-med.ac.jp
Yokoyama
Hiroki
H
Itoh
Hirofumi
H
Koya
Daisuke
D
Nakagawa
Atsushi
A
Nishizawa
Makoto
M
Maegawa
Hiroshi
H
Yokomaku
Yukiyo
Y
Araki
Shin-Ichi
S
Abiko
Atsuko
A
Haneda
Masakazu
M
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D020382:Interleukin-18 / Q000097:blood*; D019518:Postprandial Period
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D020382:Interleukin-18; C045621:miglitol; D017485:1-Deoxynojirimycin
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