Skip to main content
Top
Published in: Clinical and Experimental Nephrology 1/2011

01-02-2011 | Original Article

Elevated serum levels of interleukin-18 in patients with overt diabetic nephropathy: effects of miglitol

Authors: Takashi Uzu, Hiroki Yokoyama, Hirofumi Itoh, Daisuke Koya, Atsushi Nakagawa, Makoto Nishizawa, Hiroshi Maegawa, Yukiyo Yokomaku, Shin-ichi Araki, Atsuko Abiko, Masakazu Haneda

Published in: Clinical and Experimental Nephrology | Issue 1/2011

Login to get access

Abstract

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.

Conclusion

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.
Literature
1.
2.
go back to reference Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology and management. JAMA. 2002;2002:2570–81.CrossRef Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology and management. JAMA. 2002;2002:2570–81.CrossRef
3.
go back to reference Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63:225–32.CrossRefPubMed Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63:225–32.CrossRefPubMed
5.
go back to reference Puren AJ, Fantuzzi G, Gu Y, Su MS, Dinarello CA. Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells. J Clin Invest. 1998;101:711–21.CrossRefPubMed Puren AJ, Fantuzzi G, Gu Y, Su MS, Dinarello CA. Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells. J Clin Invest. 1998;101:711–21.CrossRefPubMed
6.
go back to reference Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schönbeck U, Khera A, et al. Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis: results from the Dallas Heart Study. Arterioscler Thromb Vasc Biol. 2007;27:2043–9.CrossRefPubMed Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schönbeck U, Khera A, et al. Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis: results from the Dallas Heart Study. Arterioscler Thromb Vasc Biol. 2007;27:2043–9.CrossRefPubMed
7.
go back to reference Everett BM, Bansal S, Rifai N, Buring JEPMR. Interleukin-18 and the risk of future cardiovascular disease among initially healthy women. Atherosclerosis. 2009;202:282–8.CrossRefPubMed Everett BM, Bansal S, Rifai N, Buring JEPMR. Interleukin-18 and the risk of future cardiovascular disease among initially healthy women. Atherosclerosis. 2009;202:282–8.CrossRefPubMed
8.
go back to reference Skopiński P, Rogala E, Duda-Król B, Lipińska A, Sommer E, Chorostowska-Wynimko J. Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. J Diabetes Complicat. 2005;19:335–8.CrossRefPubMed Skopiński P, Rogala E, Duda-Król B, Lipińska A, Sommer E, Chorostowska-Wynimko J. Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. J Diabetes Complicat. 2005;19:335–8.CrossRefPubMed
9.
go back to reference Nakamura A, Shikata K, Hiramatsu M, Nakatou T, Kitamura T, Wada J, et al. Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Care. 2005;28:2890–5.CrossRefPubMed Nakamura A, Shikata K, Hiramatsu M, Nakatou T, Kitamura T, Wada J, et al. Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Care. 2005;28:2890–5.CrossRefPubMed
10.
go back to reference Araki S, Haneda M, Koya D, Sugimoto T, Isshiki K, Chin-Kanasaki M, et al. Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study. Diabetologia. 2007;50:867–73.CrossRefPubMed Araki S, Haneda M, Koya D, Sugimoto T, Isshiki K, Chin-Kanasaki M, et al. Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study. Diabetologia. 2007;50:867–73.CrossRefPubMed
11.
go back to reference Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, et al. Management of hyperglycemia in Type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:1963–72.CrossRefPubMed Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, et al. Management of hyperglycemia in Type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:1963–72.CrossRefPubMed
12.
go back to reference Ceriello A, Colagiuri S. International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations. Diabet Med. 2008;25:1151–6.CrossRefPubMed Ceriello A, Colagiuri S. International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations. Diabet Med. 2008;25:1151–6.CrossRefPubMed
13.
go back to reference Fischer CP, Perstrup LB, Berntsen A, Eskildsen P, Pedersen BK. Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. Clin Immunol. 2005;117:152–60.CrossRefPubMed Fischer CP, Perstrup LB, Berntsen A, Eskildsen P, Pedersen BK. Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. Clin Immunol. 2005;117:152–60.CrossRefPubMed
14.
go back to reference Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, et al. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab. 2007;92:4569–74.CrossRefPubMed Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, et al. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab. 2007;92:4569–74.CrossRefPubMed
15.
go back to reference Altinova AE, Yetkin I, Akbay E, Bukan N, Arslan M. Serum IL-18 levels in patients with type 1 diabetes: relations to metabolic control and microvascular complications. Cytokine. 2008;42:217–21.CrossRefPubMed Altinova AE, Yetkin I, Akbay E, Bukan N, Arslan M. Serum IL-18 levels in patients with type 1 diabetes: relations to metabolic control and microvascular complications. Cytokine. 2008;42:217–21.CrossRefPubMed
16.
go back to reference Ahr HJ, Boberg M, Brendel E, Krause HP, Steinke W. Pharmacokinetics of miglitol Absorption, distribution, metabolism, and excretion following administration to rats, dogs, and man. Arzneimittelforschung. 1997;47:734–45.PubMed Ahr HJ, Boberg M, Brendel E, Krause HP, Steinke W. Pharmacokinetics of miglitol Absorption, distribution, metabolism, and excretion following administration to rats, dogs, and man. Arzneimittelforschung. 1997;47:734–45.PubMed
17.
go back to reference Guerrant GO, Moss CW. Determination of monosaccharides as aldononitrile, o-methyloxime, alditol, and cyclitol acetate derivatives by gas chromatography. Anal Chem. 1984;56:633–8.CrossRef Guerrant GO, Moss CW. Determination of monosaccharides as aldononitrile, o-methyloxime, alditol, and cyclitol acetate derivatives by gas chromatography. Anal Chem. 1984;56:633–8.CrossRef
18.
go back to reference Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed
19.
go back to reference Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001;37:1053–9.PubMed Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001;37:1053–9.PubMed
20.
21.
go back to reference Mallat Z, Corbaz A, Scoazec A, Besnard S, Lesèche G, Chvatchko Y, et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation. 2001;104:1598–603.CrossRefPubMed Mallat Z, Corbaz A, Scoazec A, Besnard S, Lesèche G, Chvatchko Y, et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation. 2001;104:1598–603.CrossRefPubMed
22.
go back to reference Welsh P, Woodward M, Rumley A, Lowe G. Associations of circulating TNFalpha and IL-18 with myocardial infarction and cardiovascular risk markers: the Glasgow Myocardial Infarction Study. Cytokine. 2009;47:143–7.CrossRefPubMed Welsh P, Woodward M, Rumley A, Lowe G. Associations of circulating TNFalpha and IL-18 with myocardial infarction and cardiovascular risk markers: the Glasgow Myocardial Infarction Study. Cytokine. 2009;47:143–7.CrossRefPubMed
23.
go back to reference Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111–9.PubMed Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111–9.PubMed
24.
go back to reference Dickhout JG, Krepinsky JC. Endoplasmic reticulum stress and renal disease. Antioxid Redox Signal. 2009;11:2341–52.CrossRefPubMed Dickhout JG, Krepinsky JC. Endoplasmic reticulum stress and renal disease. Antioxid Redox Signal. 2009;11:2341–52.CrossRefPubMed
25.
go back to reference Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.CrossRefPubMed Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.CrossRefPubMed
26.
go back to reference Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martín J, et al. L-18 regulates IL-1β-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. PNAS. 2000;97:734–9.CrossRefPubMed Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martín J, et al. L-18 regulates IL-1β-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. PNAS. 2000;97:734–9.CrossRefPubMed
27.
go back to reference Berneis K, Rizzo M, Evans J, Rini GB, Spinas GA, Goedecke JH. Interleukin-18 levels are associated with low-density lipoproteins size. Eur J Clin Invest. 2010;40:54–5.CrossRefPubMed Berneis K, Rizzo M, Evans J, Rini GB, Spinas GA, Goedecke JH. Interleukin-18 levels are associated with low-density lipoproteins size. Eur J Clin Invest. 2010;40:54–5.CrossRefPubMed
28.
go back to reference Porazko T, Kúzniar J, Kusztal M, Kúzniar TJ, Weyde W, Kuriata-Kordek M, et al. IL-18 is involved in vascular injury in end-stage renal disease patients. Nephrol Dial Transplant. 2009;24:589–96.CrossRefPubMed Porazko T, Kúzniar J, Kusztal M, Kúzniar TJ, Weyde W, Kuriata-Kordek M, et al. IL-18 is involved in vascular injury in end-stage renal disease patients. Nephrol Dial Transplant. 2009;24:589–96.CrossRefPubMed
29.
go back to reference UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1999;12:703–13. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1999;12:703–13.
30.
go back to reference American Diabetes Association. Standards of medical care in diabetes––2009. Diabetes Care. 2009;2009(Suppl 1):S13–61.CrossRef American Diabetes Association. Standards of medical care in diabetes––2009. Diabetes Care. 2009;2009(Suppl 1):S13–61.CrossRef
31.
go back to reference Charpentier G, Riveline JP, Varroud-Vial M. Management of drugs affecting blood glucose in diabetic patients with renal failure. Diabetes Metab. 2000;26(Suppl4):73–85.PubMed Charpentier G, Riveline JP, Varroud-Vial M. Management of drugs affecting blood glucose in diabetic patients with renal failure. Diabetes Metab. 2000;26(Suppl4):73–85.PubMed
32.
go back to reference Baer DJ, Judd JT, Clevidence BA, Tracy RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. Am J Clin Nutr. 2004;79:969–73.PubMed Baer DJ, Judd JT, Clevidence BA, Tracy RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. Am J Clin Nutr. 2004;79:969–73.PubMed
33.
go back to reference Ghanim H, Abuaysheh S, Sia CL, Korzeniewski K, Chaudhuri A, Fernandez-Real JM. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009;32:2281–7.CrossRefPubMed Ghanim H, Abuaysheh S, Sia CL, Korzeniewski K, Chaudhuri A, Fernandez-Real JM. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009;32:2281–7.CrossRefPubMed
34.
go back to reference Arakawa M, Ebato C, Mita T, Fujitani Y, Shimizu T, Watada H, et al. Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects. Metabolism. 2008;57:1299–306.CrossRefPubMed Arakawa M, Ebato C, Mita T, Fujitani Y, Shimizu T, Watada H, et al. Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects. Metabolism. 2008;57:1299–306.CrossRefPubMed
35.
go back to reference Assaloni R, Da Ros R, Quagliaro L, Piconi L, Maier A, Zuodar G, et al. Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients. Diabetologia. 2005;48:1919–24.CrossRefPubMed Assaloni R, Da Ros R, Quagliaro L, Piconi L, Maier A, Zuodar G, et al. Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients. Diabetologia. 2005;48:1919–24.CrossRefPubMed
Metadata
Title
Elevated serum levels of interleukin-18 in patients with overt diabetic nephropathy: effects of miglitol
Authors
Takashi Uzu
Hiroki Yokoyama
Hirofumi Itoh
Daisuke Koya
Atsushi Nakagawa
Makoto Nishizawa
Hiroshi Maegawa
Yukiyo Yokomaku
Shin-ichi Araki
Atsuko Abiko
Masakazu Haneda
Publication date
01-02-2011
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 1/2011
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-010-0343-7

Other articles of this Issue 1/2011

Clinical and Experimental Nephrology 1/2011 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.