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Published in: Clinical Drug Investigation 8/2013

01-08-2013 | Original Research Article

Effects of Mitiglinide, a Short-Acting Insulin Secretagogue, on Daily Glycemic Variability and Oxidative Stress Markers in Japanese Patients with Type 2 Diabetes Mellitus

Authors: Noriko Kodani, Yoshifumi Saisho, Kumiko Tanaka, Toshihide Kawai, Hiroshi Itoh

Published in: Clinical Drug Investigation | Issue 8/2013

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Abstract

Background and Objective

The objective of this study was to clarify the effects of mitiglinide on daily glycemic variability and oxidative stress markers in outpatients with type 2 diabetes mellitus that is insufficiently controlled by diet and/or non-insulin secretagogues.

Methods

We enrolled 24 patients with type 2 diabetes whose glycemic control had been suboptimal [i.e. glycosylated hemoglobin (HbA1c) ≥6.9 %]. The patients were treated with mitiglinide 10 mg three times daily for 16 weeks. If their glycemic control was not improved at week 8, the dose of mitiglinide was increased to 20 mg three times daily. Daily glycemic variability was assessed by 7-point self-monitoring of blood glucose for 2 days, and standard deviation (SD), M value, and mean of daily differences (MODD) were calculated. Oxidative stress was assessed by oxidized low-density lipoprotein, pentosidine, urinary 8-iso-prostaglandin F2alpha, and urinary 8-hydroxydeoxy guanosine.

Results

After 16 weeks of mitiglinide treatment, the HbA1c level was significantly decreased (mean ± SD, 7.4 ± 0.7 to 6.8 ± 0.5 %, P < 0.0001). Postprandial glucose excursion and glycemic variability were also significantly improved after mitiglinide treatment (all P < 0.05). The reductions in SD, M value, and MODD were 17, 50, and 48 %, respectively. There was a significant positive correlation between the change in HbA1c and change in SD during the study (r = 0.454, P = 0.03). There were no significant changes in oxidative stress markers.

Conclusions

The present study supports the notion that mitiglinide improves postprandial glucose excursion and HbA1c level in patients with type 2 diabetes. In addition, we demonstrated that mitiglinide also effectively improves daily glycemic variability. The effect of mitiglinide on oxidative stress needs further investigation.
Literature
2.
go back to reference Saito I. Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan. Circ J. 2012;76:1066–73.PubMedCrossRef Saito I. Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan. Circ J. 2012;76:1066–73.PubMedCrossRef
3.
go back to reference DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161:397–405.CrossRef DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161:397–405.CrossRef
4.
go back to reference DECODA Study Group, International Diabetes Epidemiology Group. Cardiovascular risk profile assessment in glucose-intolerant Asian individuals—an evaluation of the World Health Organization two-step strategy: the DECODA study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia). Diabet Med. 2002;19:549–57.CrossRef DECODA Study Group, International Diabetes Epidemiology Group. Cardiovascular risk profile assessment in glucose-intolerant Asian individuals—an evaluation of the World Health Organization two-step strategy: the DECODA study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia). Diabet Med. 2002;19:549–57.CrossRef
5.
go back to reference Cavalot F, Petrelli A, Traversa M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab. 2006;91:813–9.PubMedCrossRef Cavalot F, Petrelli A, Traversa M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab. 2006;91:813–9.PubMedCrossRef
6.
go back to reference Tominaga M, Eguchi H, Manaka H, et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999;22:920–4.PubMedCrossRef Tominaga M, Eguchi H, Manaka H, et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999;22:920–4.PubMedCrossRef
7.
go back to reference Nakagami T, The DECODA Study Group. Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia. 2004;47:385–94.PubMedCrossRef Nakagami T, The DECODA Study Group. Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia. 2004;47:385–94.PubMedCrossRef
8.
9.
go back to reference Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106:2067–72.PubMedCrossRef Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106:2067–72.PubMedCrossRef
10.
go back to reference Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 2003;26:1589–96.PubMedCrossRef Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 2003;26:1589–96.PubMedCrossRef
11.
go back to reference Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681–7.PubMedCrossRef Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681–7.PubMedCrossRef
12.
go back to reference Kaiser N, Nesher R, Oprescu A, et al. Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic beta-cells. Br J Pharmacol. 2005;146:872–81.PubMedCrossRef Kaiser N, Nesher R, Oprescu A, et al. Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic beta-cells. Br J Pharmacol. 2005;146:872–81.PubMedCrossRef
13.
go back to reference Konya H, Miuchi M, Konishi K, et al. Pleiotropic effects of mitiglinide in type 2 diabetes mellitus. J Int Med Res. 2009;37:1904–12.PubMedCrossRef Konya H, Miuchi M, Konishi K, et al. Pleiotropic effects of mitiglinide in type 2 diabetes mellitus. J Int Med Res. 2009;37:1904–12.PubMedCrossRef
14.
go back to reference Pratley RE, Foley JE, Dunning BE. Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiologic approach to improve glucose control. Curr Pharm Des. 2001;7:1375–97.PubMedCrossRef Pratley RE, Foley JE, Dunning BE. Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiologic approach to improve glucose control. Curr Pharm Des. 2001;7:1375–97.PubMedCrossRef
15.
go back to reference Ohnota H, Koizumi T, Tsutsumi N, et al. Novel rapid- and short-acting hypoglycemic agent, a calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) that acts on the sulfonylurea receptor: comparison of effects between KAD-1229 and gliclazide. J Pharmacol Exp Ther. 1994;269:489–95.PubMed Ohnota H, Koizumi T, Tsutsumi N, et al. Novel rapid- and short-acting hypoglycemic agent, a calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) that acts on the sulfonylurea receptor: comparison of effects between KAD-1229 and gliclazide. J Pharmacol Exp Ther. 1994;269:489–95.PubMed
16.
go back to reference Assaloni R, Da Ros R, Quagliaro L, et al. Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients. Diabetologia. 2005;48:1919–24.PubMedCrossRef Assaloni R, Da Ros R, Quagliaro L, et al. Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients. Diabetologia. 2005;48:1919–24.PubMedCrossRef
17.
go back to reference Kashiwagi A, Kasuga M, Araki E, et al. International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J Diabetes Investig. 2012;2012(3):39–40.CrossRef Kashiwagi A, Kasuga M, Araki E, et al. International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J Diabetes Investig. 2012;2012(3):39–40.CrossRef
18.
go back to reference Yoshiuchi K, Matsuhisa M, Katakami N, et al. Glycated albumin is a better indicator for glucose excursion than glycated hemoglobin in type 1 and type 2 diabetes. Endocr J. 2008;55:503–7.PubMedCrossRef Yoshiuchi K, Matsuhisa M, Katakami N, et al. Glycated albumin is a better indicator for glucose excursion than glycated hemoglobin in type 1 and type 2 diabetes. Endocr J. 2008;55:503–7.PubMedCrossRef
19.
go back to reference Saisho Y, Tanaka K, Abe T, et al. Glycated albumin to glycated hemoglobin ratio reflects postprandial glucose excursion and relates to beta cell function in both type 1 and type 2 diabetes. Diabetol Int. 2011;2:146–53.CrossRef Saisho Y, Tanaka K, Abe T, et al. Glycated albumin to glycated hemoglobin ratio reflects postprandial glucose excursion and relates to beta cell function in both type 1 and type 2 diabetes. Diabetol Int. 2011;2:146–53.CrossRef
20.
go back to reference Nakano M, Kawanishi Y, Kamohara S, et al. Oxidative DNA damage (8-hydroxydeoxyguanosine) and body iron status: a study on 2507 healthy people. Free Radic Biol Med. 2003;35:826–32.PubMedCrossRef Nakano M, Kawanishi Y, Kamohara S, et al. Oxidative DNA damage (8-hydroxydeoxyguanosine) and body iron status: a study on 2507 healthy people. Free Radic Biol Med. 2003;35:826–32.PubMedCrossRef
21.
go back to reference Schlichtkrull J, Munck O, Jersild M. The M-valve, an index of blood sugar control in diabetics. Acta Med Scand. 1965;177:95–102.PubMedCrossRef Schlichtkrull J, Munck O, Jersild M. The M-valve, an index of blood sugar control in diabetics. Acta Med Scand. 1965;177:95–102.PubMedCrossRef
22.
go back to reference Molnar GD, Taylor WF, Ho MM. Day-to-day variation of continuously monitored glycaemia: a further measure of diabetic instability. Diabetologia. 1972;8:342–8.PubMedCrossRef Molnar GD, Taylor WF, Ho MM. Day-to-day variation of continuously monitored glycaemia: a further measure of diabetic instability. Diabetologia. 1972;8:342–8.PubMedCrossRef
23.
go back to reference Saisho Y, Shimada A, Kawai T, et al. Effectiveness of switching from mitiglinide 30 mg or nateglinide 270 mg daily to mitiglinide 60 mg daily on glycemic control and body weight in type 2 diabetic patients. J New Rem Clin. 2010;59:950–9. Saisho Y, Shimada A, Kawai T, et al. Effectiveness of switching from mitiglinide 30 mg or nateglinide 270 mg daily to mitiglinide 60 mg daily on glycemic control and body weight in type 2 diabetic patients. J New Rem Clin. 2010;59:950–9.
24.
go back to reference Gao X. Multicentre, double-blind, randomized study of mitiglinide compared with nateglinide in type 2 diabetes mellitus patients in China. J Int Med Res. 2009;37:812–21.PubMedCrossRef Gao X. Multicentre, double-blind, randomized study of mitiglinide compared with nateglinide in type 2 diabetes mellitus patients in China. J Int Med Res. 2009;37:812–21.PubMedCrossRef
25.
go back to reference Kaku K, Tanaka S, Origasa H, et al. Effect of mitiglinide on glycemic control over 52 weeks in Japanese type 2 diabetic patients insufficiently controlled with pioglitazone monotherapy. Endocr J. 2009;56:739–46.PubMedCrossRef Kaku K, Tanaka S, Origasa H, et al. Effect of mitiglinide on glycemic control over 52 weeks in Japanese type 2 diabetic patients insufficiently controlled with pioglitazone monotherapy. Endocr J. 2009;56:739–46.PubMedCrossRef
26.
go back to reference Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract. 2006;12(Suppl 1):25–30.PubMedCrossRef Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract. 2006;12(Suppl 1):25–30.PubMedCrossRef
27.
go back to reference Hanefeld M, Cagatay M, Petrowitsch T, et al. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004;25:10–6.PubMedCrossRef Hanefeld M, Cagatay M, Petrowitsch T, et al. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004;25:10–6.PubMedCrossRef
28.
go back to reference Esposito K, Ciotola M, Carleo D, et al. Post-meal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes. J Clin Endocrinol Metab. 2008;93:1345–50.PubMedCrossRef Esposito K, Ciotola M, Carleo D, et al. Post-meal glucose peaks at home associate with carotid intima-media thickness in type 2 diabetes. J Clin Endocrinol Metab. 2008;93:1345–50.PubMedCrossRef
29.
go back to reference Ceriello A, Esposito K, Piconi L, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008;57:1349–54.PubMedCrossRef Ceriello A, Esposito K, Piconi L, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008;57:1349–54.PubMedCrossRef
30.
go back to reference Kondo A, Manabe M, Saito K, et al. Insulin treatment prevents LDL from accelerated oxidation in patients with diabetes. J Atheroscler Thromb. 2002;9:280–7.PubMedCrossRef Kondo A, Manabe M, Saito K, et al. Insulin treatment prevents LDL from accelerated oxidation in patients with diabetes. J Atheroscler Thromb. 2002;9:280–7.PubMedCrossRef
31.
go back to reference Su Y, Xu Y, Sun YM, et al. Comparison of the effects of simvastatin versus atorvastatin on oxidative stress in patients with type 2 diabetes mellitus. J Cardiovasc Pharmacol. 2010;55:21–5.PubMedCrossRef Su Y, Xu Y, Sun YM, et al. Comparison of the effects of simvastatin versus atorvastatin on oxidative stress in patients with type 2 diabetes mellitus. J Cardiovasc Pharmacol. 2010;55:21–5.PubMedCrossRef
32.
go back to reference Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRef Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRef
33.
go back to reference Monnier L, Colette C, Mas E, et al. Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy. Diabetologia. 2010;53:562–71.PubMedCrossRef Monnier L, Colette C, Mas E, et al. Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy. Diabetologia. 2010;53:562–71.PubMedCrossRef
34.
go back to reference Seaquist ER, Kahn SE, Clark PM, et al. Hyperproinsulinemia is associated with increased beta cell demand after hemipancreatectomy in humans. J Clin Investig. 1996;97:455–60.PubMedCrossRef Seaquist ER, Kahn SE, Clark PM, et al. Hyperproinsulinemia is associated with increased beta cell demand after hemipancreatectomy in humans. J Clin Investig. 1996;97:455–60.PubMedCrossRef
35.
go back to reference Inoguchi T, Umeda F, Kakimoto M, et al. Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J. 2000;47:763–70.PubMedCrossRef Inoguchi T, Umeda F, Kakimoto M, et al. Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J. 2000;47:763–70.PubMedCrossRef
Metadata
Title
Effects of Mitiglinide, a Short-Acting Insulin Secretagogue, on Daily Glycemic Variability and Oxidative Stress Markers in Japanese Patients with Type 2 Diabetes Mellitus
Authors
Noriko Kodani
Yoshifumi Saisho
Kumiko Tanaka
Toshihide Kawai
Hiroshi Itoh
Publication date
01-08-2013
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 8/2013
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-013-0098-5

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