Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2019

Open Access 01-12-2019 | Insulins | Research

Effect of rosiglitazone on inflammatory cytokines and oxidative stress after intensive insulin therapy in patients with newly diagnosed type 2 diabetes

Authors: Juan Li, Xingping Shen

Published in: Diabetology & Metabolic Syndrome | Issue 1/2019

Login to get access

Abstract

Objective

To evaluate the effect of insulin sensitizer on inflammatory cytokines and oxidative stress in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods

After intensive insulin therapy, patients with newly diagnosed T2DM were continuously treated with either insulin sensitizer or insulin for 48 weeks, and then their inflammatory cytokine and oxidative stress levels were measured.

Results

Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, hypersensitive C reactive protein (hs-CRP), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (8-iso-PGF) levels of the rosiglitazone (RSG) group and the rosiglitazone combined with metformin (RSG + metformin) group were significantly reduced after the treatments (P < 0.05). Hs-CRP, MDA, and 8-iso-PGF levels of the metformin group were significantly reduced after the treatments (P < 0.05). Superoxide dismutase (SOD) and total antioxidant capacity (TAC) were significantly increased after the treatments in all three groups (P < 0.05 and P < 0.01).

Conclusion

Early application of insulin sensitizers improved inflammation and oxidative stress in patients with newly diagnosed T2DM.
Literature
1.
go back to reference Bauduceau B, Le Floch JP, Halimi S, et al. Cardiovascular complications over 5 years and their association with survival in the GERODIAB cohort of elderly french patients with type 2 diabetes. Diabetes Care. 2018;41:156–62.CrossRefPubMed Bauduceau B, Le Floch JP, Halimi S, et al. Cardiovascular complications over 5 years and their association with survival in the GERODIAB cohort of elderly french patients with type 2 diabetes. Diabetes Care. 2018;41:156–62.CrossRefPubMed
2.
go back to reference Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol. 2015;3:105–13.CrossRefPubMedPubMedCentral Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol. 2015;3:105–13.CrossRefPubMedPubMedCentral
4.
go back to reference Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J Cell Biochem. 2017;118:3577–85.CrossRefPubMed Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J Cell Biochem. 2017;118:3577–85.CrossRefPubMed
5.
go back to reference Francisqueti FV, Chiaverini LC, Santos KC, et al. The role of oxidative stress on the pathophysiology of metabolic syndrome. Rev Assoc Med Bras. 2017;63:85–91.CrossRefPubMed Francisqueti FV, Chiaverini LC, Santos KC, et al. The role of oxidative stress on the pathophysiology of metabolic syndrome. Rev Assoc Med Bras. 2017;63:85–91.CrossRefPubMed
6.
go back to reference Evans JL, Goldfine IA, Maddux BA, et al. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrine Rev. 2002;23:599–622.CrossRef Evans JL, Goldfine IA, Maddux BA, et al. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrine Rev. 2002;23:599–622.CrossRef
7.
go back to reference Fernandez M, Triplitt C, Wajcberg E, et al. Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care. 2008;31:121–7.CrossRefPubMed Fernandez M, Triplitt C, Wajcberg E, et al. Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care. 2008;31:121–7.CrossRefPubMed
8.
go back to reference Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125–35.CrossRefPubMed Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125–35.CrossRefPubMed
9.
go back to reference Florez H, Reaven PD, Bahn G, et al. Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial. Diabetes Obes Metab. 2015;17:949–55.CrossRefPubMedPubMedCentral Florez H, Reaven PD, Bahn G, et al. Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial. Diabetes Obes Metab. 2015;17:949–55.CrossRefPubMedPubMedCentral
13.
go back to reference Malínská H, Oliyarnyk O, Škop V, et al. Effects of metformin on tissue oxidative and dicarbonyl stress in transgenic spontaneously hypertensive rats expressing human C-reactive protein. PLoS ONE. 2016;11(3):e0150924.CrossRefPubMedPubMedCentral Malínská H, Oliyarnyk O, Škop V, et al. Effects of metformin on tissue oxidative and dicarbonyl stress in transgenic spontaneously hypertensive rats expressing human C-reactive protein. PLoS ONE. 2016;11(3):e0150924.CrossRefPubMedPubMedCentral
14.
go back to reference Pruski M, Krysiak R, Okopien B. Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia. Diabetes Care. 2009;32:1421–4.CrossRefPubMedPubMedCentral Pruski M, Krysiak R, Okopien B. Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia. Diabetes Care. 2009;32:1421–4.CrossRefPubMedPubMedCentral
15.
go back to reference Kender Z, Fleming T, Kopf S, et al. Effect of metformin on methylglyoxal metabolism in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2014;122:316–9.CrossRefPubMed Kender Z, Fleming T, Kopf S, et al. Effect of metformin on methylglyoxal metabolism in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2014;122:316–9.CrossRefPubMed
16.
go back to reference Bailey CJ. Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones. Diabetes Obes Metab. 2005;7:675–91.CrossRefPubMed Bailey CJ. Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones. Diabetes Obes Metab. 2005;7:675–91.CrossRefPubMed
17.
go back to reference Rodney A, Hayward RA, Reaven PD, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372:2197–206.CrossRef Rodney A, Hayward RA, Reaven PD, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372:2197–206.CrossRef
18.
19.
22.
go back to reference Kern PA, Ranganathan S, Li C, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280:E745–51.CrossRefPubMed Kern PA, Ranganathan S, Li C, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280:E745–51.CrossRefPubMed
23.
go back to reference Engin A. ThePathogenesis of obesity-associated adipose tissue inflammation. Adv Exp Med Biol. 2017;960:221–45.CrossRefPubMed Engin A. ThePathogenesis of obesity-associated adipose tissue inflammation. Adv Exp Med Biol. 2017;960:221–45.CrossRefPubMed
24.
go back to reference Kaptoge S, Seshasai SR, Gao P, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. 2014;35:578–89.CrossRefPubMed Kaptoge S, Seshasai SR, Gao P, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. 2014;35:578–89.CrossRefPubMed
25.
go back to reference Esser N, Paquot N, Scheen AJ. Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert Opin Investig Drugs. 2015;24:283–307.CrossRefPubMed Esser N, Paquot N, Scheen AJ. Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert Opin Investig Drugs. 2015;24:283–307.CrossRefPubMed
26.
go back to reference Assy N, Grozovski M, Bersudsky I, et al. Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease. World J Gastroenterol. 2006;21(12):4369–76.CrossRef Assy N, Grozovski M, Bersudsky I, et al. Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease. World J Gastroenterol. 2006;21(12):4369–76.CrossRef
27.
go back to reference Arai M, Uchiba M, Komura H, et al. Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro. J Pharmacol Exp Ther. 2010;334:206–13.CrossRefPubMed Arai M, Uchiba M, Komura H, et al. Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro. J Pharmacol Exp Ther. 2010;334:206–13.CrossRefPubMed
28.
go back to reference Cullen E, Liao J, Lukacsko P, et al. Pharmacokinetics and dose proportionality of extended—release metformin following administration of 1000, 1500, 2000, and 2500 mg in healthy volunteers. Biopharm Drug Dispos. 2004;25:261–3.CrossRefPubMed Cullen E, Liao J, Lukacsko P, et al. Pharmacokinetics and dose proportionality of extended—release metformin following administration of 1000, 1500, 2000, and 2500 mg in healthy volunteers. Biopharm Drug Dispos. 2004;25:261–3.CrossRefPubMed
29.
go back to reference Pal M, Febbraio MA, Whitham M. From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation. Immunol Cell Biol. 2014;92:331–9.CrossRefPubMed Pal M, Febbraio MA, Whitham M. From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation. Immunol Cell Biol. 2014;92:331–9.CrossRefPubMed
30.
go back to reference Harder-Lauridsen NM, Krogh-Madsen R, Holst JJ, et al. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes. Am J Physiol. 2014;306:E769–78. Harder-Lauridsen NM, Krogh-Madsen R, Holst JJ, et al. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes. Am J Physiol. 2014;306:E769–78.
31.
go back to reference Lowe G, Woodward M, Hillis G, et al. Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. Diabetes. 2014;63:1115–23.CrossRefPubMed Lowe G, Woodward M, Hillis G, et al. Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. Diabetes. 2014;63:1115–23.CrossRefPubMed
32.
go back to reference Kadoglou NPE, Kapelouzou A, Tsanikidis H, et al. Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naïve patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2011;119:63–8.CrossRefPubMed Kadoglou NPE, Kapelouzou A, Tsanikidis H, et al. Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naïve patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2011;119:63–8.CrossRefPubMed
33.
go back to reference Erem C, Ozbas HM, Nuhoglu I, et al. Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2014;122:295–302.CrossRefPubMed Erem C, Ozbas HM, Nuhoglu I, et al. Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2014;122:295–302.CrossRefPubMed
34.
go back to reference Borowska M, Dworacka M, Wesołowska A, et al. The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1β, IL-6 and IL-10 Secretion. Pharmacology. 2016;97:189–94.CrossRefPubMed Borowska M, Dworacka M, Wesołowska A, et al. The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1β, IL-6 and IL-10 Secretion. Pharmacology. 2016;97:189–94.CrossRefPubMed
35.
go back to reference Wang J, Zhu L, Hu K, et al. Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis. Medicine (Baltimore). 2017;96(39):e8183.CrossRefPubMedPubMedCentral Wang J, Zhu L, Hu K, et al. Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis. Medicine (Baltimore). 2017;96(39):e8183.CrossRefPubMedPubMedCentral
36.
go back to reference Besedovsky HO, Rey AD. Physiologic versus diabetogenic effects of interleukin- 1: a question of weight. Curr Pharm Des. 2014;20:4733–40.CrossRefPubMed Besedovsky HO, Rey AD. Physiologic versus diabetogenic effects of interleukin- 1: a question of weight. Curr Pharm Des. 2014;20:4733–40.CrossRefPubMed
37.
go back to reference Mooradian AD, Reed RL, Meredith KE, Scuderi P. Serum levels of tumor necrosis factor and IL-1 alpha and IL-1 beta in diabetic patients. Diabetes Care. 1991;14:63–5.CrossRefPubMed Mooradian AD, Reed RL, Meredith KE, Scuderi P. Serum levels of tumor necrosis factor and IL-1 alpha and IL-1 beta in diabetic patients. Diabetes Care. 1991;14:63–5.CrossRefPubMed
38.
go back to reference Ohkuma T, Jun M, Woodward M, et al. Cardiac stress and inflammatory markers as predictors of heart failure in patients with type 2 diabetes: the Advance Trial. Diabetes Care. 2017;40:1203–9.CrossRefPubMedPubMedCentral Ohkuma T, Jun M, Woodward M, et al. Cardiac stress and inflammatory markers as predictors of heart failure in patients with type 2 diabetes: the Advance Trial. Diabetes Care. 2017;40:1203–9.CrossRefPubMedPubMedCentral
39.
go back to reference Kahn SE, Haffner SM, Viberti G, et al. Rosiglitazone decreases C-reactive protein to a greater extent relative to glyburide and metformin over 4 years despite greater weight gain. Diabetes Care. 2010;33:177–83.CrossRefPubMed Kahn SE, Haffner SM, Viberti G, et al. Rosiglitazone decreases C-reactive protein to a greater extent relative to glyburide and metformin over 4 years despite greater weight gain. Diabetes Care. 2010;33:177–83.CrossRefPubMed
40.
go back to reference Takebayashi K, Aso Y, Inukai T. Initiation of insulin therapy reduces serum concentrations of high-sensitivity C- reactive protein in patients with type 2 diabetes. Metabolism. 2004;53:693–9.CrossRefPubMed Takebayashi K, Aso Y, Inukai T. Initiation of insulin therapy reduces serum concentrations of high-sensitivity C- reactive protein in patients with type 2 diabetes. Metabolism. 2004;53:693–9.CrossRefPubMed
41.
go back to reference Pradhan AD, Everett BM, Cook NR, et al. Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial. JAMA. 2009;302:1186–94.CrossRefPubMed Pradhan AD, Everett BM, Cook NR, et al. Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial. JAMA. 2009;302:1186–94.CrossRefPubMed
42.
go back to reference Khatana SA, Taveira TH, Dooley AG, et al. The association between C-reactive protein levels and insulin therapy in obese vs nonobese veterans with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2010;12:462–8.CrossRef Khatana SA, Taveira TH, Dooley AG, et al. The association between C-reactive protein levels and insulin therapy in obese vs nonobese veterans with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2010;12:462–8.CrossRef
43.
go back to reference Huang ML, Que YY, Shen XP. Correlation of the plasma levels of soluble RAGE and endogenous secretory RAGE with oxidative stress in pre-diabetic patients. J Diabetes Compl. 2015;29:422–6.CrossRef Huang ML, Que YY, Shen XP. Correlation of the plasma levels of soluble RAGE and endogenous secretory RAGE with oxidative stress in pre-diabetic patients. J Diabetes Compl. 2015;29:422–6.CrossRef
44.
go back to reference He H, Tao H, Xiong H, et al. Rosiglitazone causes cardiotoxicity via peroxisome proliferator-activated receptorγ-independent mitochondrial oxidative stress in mouse hearts. Toxicol Sci. 2014;138:468–81.CrossRefPubMedPubMedCentral He H, Tao H, Xiong H, et al. Rosiglitazone causes cardiotoxicity via peroxisome proliferator-activated receptorγ-independent mitochondrial oxidative stress in mouse hearts. Toxicol Sci. 2014;138:468–81.CrossRefPubMedPubMedCentral
45.
go back to reference Calkin AC, Forbes JM, Smith CM, et al. Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects. Arterioscler Thromb Vasc Biol. 2005;25:1903–9.CrossRefPubMed Calkin AC, Forbes JM, Smith CM, et al. Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects. Arterioscler Thromb Vasc Biol. 2005;25:1903–9.CrossRefPubMed
46.
go back to reference Barroso I, Gurnell M, Crowley VE, et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402:880–3.CrossRefPubMed Barroso I, Gurnell M, Crowley VE, et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402:880–3.CrossRefPubMed
47.
go back to reference Grey ST, Mackay F, et al. Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. Endocrinology. 2007;148:346–53.CrossRefPubMed Grey ST, Mackay F, et al. Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. Endocrinology. 2007;148:346–53.CrossRefPubMed
48.
go back to reference Chen Q, Yu W, Shi JL, et al. Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats. J Inflamm (Lond). 2014;11:18.CrossRef Chen Q, Yu W, Shi JL, et al. Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats. J Inflamm (Lond). 2014;11:18.CrossRef
49.
go back to reference Paneni F, Beckman JA, Creager MA, et al. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J. 2013;34:2436–46.CrossRefPubMedPubMedCentral Paneni F, Beckman JA, Creager MA, et al. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J. 2013;34:2436–46.CrossRefPubMedPubMedCentral
50.
go back to reference Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–71.CrossRefPubMed Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–71.CrossRefPubMed
51.
go back to reference LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2019;104:1520–74.CrossRefPubMed LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2019;104:1520–74.CrossRefPubMed
Metadata
Title
Effect of rosiglitazone on inflammatory cytokines and oxidative stress after intensive insulin therapy in patients with newly diagnosed type 2 diabetes
Authors
Juan Li
Xingping Shen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2019
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-019-0432-z

Other articles of this Issue 1/2019

Diabetology & Metabolic Syndrome 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
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