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Published in: Diabetology & Metabolic Syndrome 1/2016

Open Access 01-12-2016 | Research

Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study

Authors: Glauce Cordeiro Ulhôa Tostes, Maria Rosário Cunha, Rosa Tsumeshiro Fukui, Márcia Regina Silva Correia, Dalva Marreiro Rocha, Rosa Ferreira dos Santos, Maria Elizabeth Rossi da Silva

Published in: Diabetology & Metabolic Syndrome | Issue 1/2016

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Abstract

Background

To compare the effects of nateglinide and rosiglitazone on inflammatory markers, GLP-1 levels and metabolic profile in patients with type 2 diabetes (DM2).

Methods

A prospective study was performed in 20 patients with DM2, mean age 51.82 ± 8.05 years, previously treated with dietary intervention. Participants were randomized into rosiglitazone (4–8 mg/day) or nateglinide (120 mg 3 times a day) therapy. After 4 months, the patients were crossed-over with 8 weeks washout period to the alternative treatment for an additional 4-month period on similar dosage schedule. The following variables were assessed before and after 4 months of each treatment period: (1) a test with a standardized 500 calories meal for 5 h including frequent measurements of glucose, insulin, glucagon, proinsulin, GLP-1, free fat acids (FFA), and triglycerides levels was obtained. The lipid profile and HbA1 levels were measured at fasting. (2) Haemostatic and inflammatory markers: platelet aggregation, fibrinogen, PAI-1 activity, C reactive protein (CRP), IL-6, TNF-α, leptin, sICAM and TGFβ levels.

Results

Both therapy decreased blood glucose levels under the postprandial curve but neither affected glucagon and GLP-1 levels. Nateglinide was associated with higher insulin and pro-insulin secretion, but similar pro-insulin/insulin ratio when compared with rosiglitazone. Only rosiglitazone decreased Homa β, PAI-1 activity, CRP, fibrinogen, TGFβ, FFA and triglyceride levels.

Conclusions

Nateglinide and rosiglitazone were effective in improving glucose and lipid profile and β cell function, but rosiglitazone afforded a better anti-inflammatory effect. No drug restored alpha cell sensitivity or changed GLP-1 levels. Maintenance of haemostatic factors, inflammatory factors and glucagon levels can be related to the continuously worsening of cardiovascular function and glucose control observed in DM2.
Literature
1.
go back to reference Stolar M. Glycemic control and complications in type 2 diabetes mellitus. Am J Med. 2010;123(Suppl 3):S3–11.CrossRefPubMed Stolar M. Glycemic control and complications in type 2 diabetes mellitus. Am J Med. 2010;123(Suppl 3):S3–11.CrossRefPubMed
2.
go back to reference American Diabetes Association. Standards of medical care in diabetes 2014. Diabetes Care. 2014;37(suppl 1):S14–80.CrossRef American Diabetes Association. Standards of medical care in diabetes 2014. Diabetes Care. 2014;37(suppl 1):S14–80.CrossRef
3.
go back to reference Yau H, Rivera K, Lomonaco R, Cusi K. The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep. 2013;13:329–41.CrossRefPubMed Yau H, Rivera K, Lomonaco R, Cusi K. The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep. 2013;13:329–41.CrossRefPubMed
4.
go back to reference Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med. 2001;134:61–71.CrossRefPubMed Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med. 2001;134:61–71.CrossRefPubMed
6.
go back to reference Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A, Folli F. The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci. 2013;9:936–43.CrossRefPubMedPubMedCentral Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A, Folli F. The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci. 2013;9:936–43.CrossRefPubMedPubMedCentral
7.
go back to reference Hu S. Interaction of nateglinide with K (ATP) channel in beta-cells underlies its unique insulinotropic action. Eur J Pharmacol. 2002;442:163–71.CrossRefPubMed Hu S. Interaction of nateglinide with K (ATP) channel in beta-cells underlies its unique insulinotropic action. Eur J Pharmacol. 2002;442:163–71.CrossRefPubMed
8.
go back to reference Kitahara Y, Miura K, Yasuda R, Kawanabe H, Ogawa S, Eto Y. Nateglinide stimulates glucagon-like peptide-1 release by human intestinal L cells via a K (ATP) channel-independent mechanism. Biol Pharm Bull. 2011;34:671–6.CrossRefPubMed Kitahara Y, Miura K, Yasuda R, Kawanabe H, Ogawa S, Eto Y. Nateglinide stimulates glucagon-like peptide-1 release by human intestinal L cells via a K (ATP) channel-independent mechanism. Biol Pharm Bull. 2011;34:671–6.CrossRefPubMed
9.
go back to reference Abdelmoneim AS, Hasenbank SE, Seubert JM, Brocks DR, Light PE, Simpson SH. Variations in tissue selectivity amongst insulin secretagogues: a systematic review. Diabetes Obes Metab. 2012;14:130–8.CrossRefPubMed Abdelmoneim AS, Hasenbank SE, Seubert JM, Brocks DR, Light PE, Simpson SH. Variations in tissue selectivity amongst insulin secretagogues: a systematic review. Diabetes Obes Metab. 2012;14:130–8.CrossRefPubMed
10.
go back to reference Mita T, Watada H, Shimizu T, Tamura Y, Sato F, Watanabe T, Choi JB, Hirose T, Tanaka Y, Kawamori R. Nateglinide reduces carotid intima-media thickening in type 2 diabetic patients under good glycemic control. Arterioscler Thromb Vasc Biol. 2007;27:2456–62.CrossRefPubMed Mita T, Watada H, Shimizu T, Tamura Y, Sato F, Watanabe T, Choi JB, Hirose T, Tanaka Y, Kawamori R. Nateglinide reduces carotid intima-media thickening in type 2 diabetic patients under good glycemic control. Arterioscler Thromb Vasc Biol. 2007;27:2456–62.CrossRefPubMed
11.
go back to reference Derosa G. Nateglinide does not reduce the incidence of diabetes or cardiovascular outcomes in people with impaired glucose tolerance and cardiovascular disease or risk factors. Evid Based Med. 2011;16:7–8.CrossRefPubMed Derosa G. Nateglinide does not reduce the incidence of diabetes or cardiovascular outcomes in people with impaired glucose tolerance and cardiovascular disease or risk factors. Evid Based Med. 2011;16:7–8.CrossRefPubMed
12.
go back to reference Kato, T., et al. Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study. Cardiovasc Diabetol. 2010. doi:10.1186/1475-2840-9-12. Kato, T., et al. Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study. Cardiovasc Diabetol. 2010. doi:10.​1186/​1475-2840-9-12.
14.
go back to reference Major-Pedersen A, et al. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function? Horm Metab Res. 2008;40:607–13. doi:10.1055/s-0028-1082327.CrossRefPubMed Major-Pedersen A, et al. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function? Horm Metab Res. 2008;40:607–13. doi:10.​1055/​s-0028-1082327.CrossRefPubMed
15.
go back to reference Clauss A. Rapid physiological coagulation method for determination of fibrinogen. Acta Haematol. 1957;17:237–46.CrossRefPubMed Clauss A. Rapid physiological coagulation method for determination of fibrinogen. Acta Haematol. 1957;17:237–46.CrossRefPubMed
16.
go back to reference Born GVR. Aggregation of blood platelets by adenosine diphosphate and its resersal. Nature. 1962;194:927–9.CrossRefPubMed Born GVR. Aggregation of blood platelets by adenosine diphosphate and its resersal. Nature. 1962;194:927–9.CrossRefPubMed
17.
go back to reference Singer JM, Andrade DF. Bio-environmental and public health statistics. In: Sen PK, Rao CR, editors. Analysis of longitudinal data. In Handbook of Statistics. Amsterdam: North Holland; 2000. pp. 115–60. Singer JM, Andrade DF. Bio-environmental and public health statistics. In: Sen PK, Rao CR, editors. Analysis of longitudinal data. In Handbook of Statistics. Amsterdam: North Holland; 2000. pp. 115–60.
18.
go back to reference Inoguchi T, et al. Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J. 2000;6:763–70.CrossRef Inoguchi T, et al. Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. Endocr J. 2000;6:763–70.CrossRef
20.
go back to reference Martin JH, Deacon CF, Gorrell MD, Prins JB. Incretin-based therapies—review of the physiology, pharmacology and emerging clinical experience. Intern Med J. 2011;41:299–307.CrossRefPubMed Martin JH, Deacon CF, Gorrell MD, Prins JB. Incretin-based therapies—review of the physiology, pharmacology and emerging clinical experience. Intern Med J. 2011;41:299–307.CrossRefPubMed
21.
go back to reference Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FP, et al. Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1. Eur J Pharmacol. 2007;568:278–86.CrossRefPubMed Duffy NA, Green BD, Irwin N, Gault VA, McKillop AM, O’Harte FP, et al. Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1. Eur J Pharmacol. 2007;568:278–86.CrossRefPubMed
22.
go back to reference McKillop AM, Duffy NA, Lindsay JR, Green BD, Patterson S, O’Harte FP, Bell PM, Flatt PR. Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation. Eur J Endocrinol. 2009;161:877–85.CrossRefPubMed McKillop AM, Duffy NA, Lindsay JR, Green BD, Patterson S, O’Harte FP, Bell PM, Flatt PR. Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation. Eur J Endocrinol. 2009;161:877–85.CrossRefPubMed
Metadata
Title
Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study
Authors
Glauce Cordeiro Ulhôa Tostes
Maria Rosário Cunha
Rosa Tsumeshiro Fukui
Márcia Regina Silva Correia
Dalva Marreiro Rocha
Rosa Ferreira dos Santos
Maria Elizabeth Rossi da Silva
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2016
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-015-0120-6

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