期刊论文详细信息
BMC Research Notes
The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study
Shin-ichi Taniguchi2  Kazuhiro Yamamoto1  Masahiko Kato1  Hiroko Ohkura2  Shoichiro Izawa1  Kazuhiko Matsuzawa2  Naoya Yamamoto1  Keisuke Sumi1  Hideki Shiochi1  Risa Nakanishi1  Youhei Fujioka1  Kazuoki Inoue1  Tsuyoshi Ohkura1 
[1] Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Yonago, Tottori, Japan;Department of Regional Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, Japan
关键词: Glinide;    Type 2 diabetes mellitus;    Meal tolerance test;    Proinsulin;   
Others  :  1140873
DOI  :  10.1186/1756-0500-6-453
 received in 2013-07-03, accepted in 2013-11-08,  发布年份 2013
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【 摘 要 】

Background

An elevated PI/I ratio is attributable to increased secretory demand on β-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT).

Methods

MTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride.

Results

Plasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders.

Conclusions

Mitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired β-cell function from the viewpoint of the PI/I ratio.

Trial registration

UMIN-CTR: UMIN000010467

【 授权许可】

   
2013 Ohkura et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]DeFronzo RA: Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988, 37:667-687.
  • [2]Reder ME, Porte D Jr, Schwartz RS, et al.: Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin dependent diabetes mellitus. J Clin Endocrinol Metab 1998, 83:604-608.
  • [3]Michael R, et al.: Intact proinsulin and β-cell function in lean and obese subjects with and without type 2 diabetes. Diabetes Care 1999, 22:609-614.
  • [4]Inoguchi T, Umeda F, Kakimoto M, Sako Y, Ishii H, Noda K, Kunisaki M, Imamura M, Yu HY, Etoh T, Yoshikawa H, Aoki T, Hashimoto T, Nawata H: Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J 2000, 47:763-770.
  • [5]Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, Donath MY: Sulfonylurea induced β-cell apoptosis in cultured human islets. J Clin Endocrinol Metab 2005, 90:501-506.
  • [6]Kadowaki T, Miyake Y, Kajinuma H: Risk factors for worsening to diabetes in subjects with impaired glucose tolerance. Diabetologia 1984, 26:44-49.
  • [7]Kadowaki T, Yoshinaga H: Risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM) in Japan. Diabetes Res Clin Pract 1994, 24:123-127.
  • [8]Kitasato L, Tojo T, Hatakeyama Y, Kameda R, Hashikata T, Yamaoka-Tojo M: Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide. Cardiovasc Diabetol 2012, 11:79. BioMed Central Full Text
  • [9]Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, Nanjo K, Sasaki A, Seino Y, Ito C, Shima K, Nonaka K, Kadowaki T, Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus: Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 2002, 55:65-85.
  • [10]Yoshino G, Tominaga M, Hirano T, Shiba T, Kashiwagi A, Tanaka A, Tada N, Onuma T, Egusa G, Kuwashima M, Sanke T, Oikawa S, Honda K, Tachikawa T: The test meal A:a pilot model for the international standard of test meal for an assessment of both postprandial hyperglycemia and hyperlipidemia. J Jpn Diabetes Soc 2006, 49:361-371.
  • [11]Ohkura T, Shiochi H, Fujioka Y, Sumi K, Yamamoto N, Matsuzawa K, Izawa S, Kinoshita H, Ohkura H, Kato M, Taniguchi SI, Yamamoto K: 20/(fasting C-peptide x fasting plasma glucose) is a simple and effective index of insulin resistance in patients with type 2 diabetes mellitus: a preliminary report. Cardiovasc Diabetol 2013, 12:21. BioMed Central Full Text
  • [12]Kashiwagi A, Kasuga M, Araki E, Oka Y, Hanafusa T, Ito H, Tominaga M, Oikawa S, Noda M, Kawamura T, Sanke T, Namba M, Hashiramoto M, Sasahara T, Nishio Y, Kuwa K, Ueki K, Takei I, Umemoto M, Murakami M, Yamakado M, Yatomi Y, Ohashi H: Committee on the standardization of diabetes mellitus-related laboratory testing of Japan diabetes society, “international clinical harmonization of glycated hemoglobin in Japan: from Japan diabetes society to national glycohemoglobin standardization program values. J Diabetes Invest 2012, 3:39-40.
  • [13]Seltzer HS, Allen EW, Herron AL Jr, Brennan MT: Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 1967, 46:323-335.
  • [14]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28:412-419.
  • [15]Matsuda M, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999, 22:1462-1470.
  • [16]Kawai J, Ohara-Imaizumi M, Nakamichi Y, Okamura T, Akimoto Y, Matsushima S, Aoyagi K, Kawakami H, Watanabe T, Watada H, Kawamori R, Nagamatsu S: Insulin exocytosis in Goto-Kakizaki rat beta-cells subjected to long-term glinide or sulfonylurea treatment. Biochem J 2008, 412:93-101.
  • [17]Laghmich A, Ladriere L, Malaisse-Lagae F, Malaisse WJ: Long-term effects of glibenclamide and nateglinide upon pancreatic islet function in normal and diabetic rats. Pharmacol Res 1999, 40:475-482.
  • [18]Roder ME, Porte D Jr, Schwartz RS, Kahn SE: Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997, 83:604-608.
  • [19]Assaloni R, Da Ros R, Quagliaro L, Piconi L, Maier A, Zuodar G, Motz E, Ceriello A: Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients. Diabetologia 2005, 48:1919-1924.
  • [20]Haffner SM, Mykkänen L, Valdez RA, Stern MP, Holloway DL, Monterrosa A, Bowsher RR: Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome. J Clin Endocrinol Metab 1994, 79:1806-1810.
  • [21]Pfützner A, Kunt T, Hohberg C, Mondok A, Pahler S, Konrad T, Lübben G, Forst T: Fasting intact proinsulin is a highly specific predictor of insulin resistance in type 2 diabetes. Diabetes Care 2004, 27:682-687.
  • [22]Nagi DK, Ali VM, Yudkin JS: Effect of metformin on intact proinsulin and des 31, 32 proinsulin concentrations in subjects with non’ insulin dependent (type2) diabetes mellitus. Diabetic Med 1996, 13:753-757.
  • [23]Pfützner A, Forst T: Elevated intact proinsulin levels are indicative of Beta-cell dysfunction, insulin resistance, and cardiovascular risk: impact of the antidiabetic agent pioglitazone. J Diabetes Sci Technol 2011, 5:784-793.
  • [24]Gama R, Shah S, Wright J, Marks V: Hyperinsulinaemia of hypertriglyceridaemia: a reappraisal. Diabet Med 1995, 12:321-324.
  • [25]Cooper MB, Tan KCB, Hales CN: Postprandial lipid metabolism and B-cell function in non-insulin-dependent (type 2) diabetes mellitus after mixed meals with a high fat content. Diabetic Med 1996, 13:816-827.
  • [26]Del Prato S, Tiengo A: The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab Res Rev 2001, 17:164-174.
  • [27]Pfützner A, Pfützner AH, Larbig M, Forst T: Role of intact proinsulin in diagnosis and treatment of type 2 diabetes mellitus. Diabetes Technol Ther 2004, 6:405-412.
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