Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Assaloni, Roberta; Ros, Roberto Da; Quagliaro, Lisa; Piconi, Ludovica; Maier, Amabile; Zuodar, Gianni; Motz, Enrico; Ceriello, Antonio

doi:10.1007/s00125-005-1849-5

Cited by 51 publications

(35 citation statements)

References 38 publications

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“…It has been reported that intermittent hyperglycemia (glucose spikes) induces apoptosis of vascular endothelial cells when compared with persistent hyperglycemia [13] and that mitiglinide inhibits markers of oxidative stress and inflammation caused by postprandial hyperglycemia [14]. Continuous improvement in postprandial hyperglycemia over the long term as confirmed in this study is considered highly significant clinically.…”

Section: Discussionsupporting

confidence: 63%

Effect of Mitiglinide on Glycemic Control over 52 Weeks in Japanese Type 2 Diabetic Patients Insufficiently Controlled with Pioglitazone Monotherapy

et al. 2009

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Abstract. This study was performed to examine the efficacy and safety of the rapid-and short-acting insulinotropic SUR ligand mitiglinide given as add-on therapy for 52 weeks in type 2 diabetic patients whose blood glucose was insufficiently controlled by pioglitazone monotherapy. Type 2 diabetic patients aged ≥20 years with postprandial plasma glucose (PPG1 or 2) ≥200 mg/dL and glycated hemoglobin (HbA 1C ) 6.5-<9.0% despite receiving pioglitazone 15-45 mg/day were additionally treated with concomitant mitiglinide 10 mg tid p.o. for a total treatment period of 52 weeks. In 171 patients recruited, HbA1C was significantly reduced from 7.64 ± 0.77% at baseline to 6.84 ± 0.73%, 6.64 ± 0.64%, 6.67 ± 0.57% and 6.81 ± 0.65% at weeks 16, 28, 40, and 52, respectively. Over half the patients achieved HbA 1C target of <7.0%, and one third <6.5%. Significant reductions in fasting plasma glucose (FPG) and PPG 1 and 2 hours after a meal versus baseline were noted at all time-points evaluated. The most frequently noted adverse reactions were hypoglycemic symptoms, weight gain, and peripheral edema (all mild). In type 2 diabetic patients combination therapy with mitiglinide and pioglitazone exerted significant long-term improvements in HbA 1C , FPG, and PPG and was well tolerated. This drug combination therapy is a promising means of alleviating insufficient pancreatic insulin secretion and insulin resistance. TYPE 2 diabetes mellitus is a syndrome involving insufficient insulin secretion from pancreatic β-cells and insulin resistance in peripheral tissues [1]. Patients with this disease often have postprandial hyperglycemia because rapid additional secretion of insulin after meals is insufficient, and a vicious circle of glucotoxicity leading to protracted and advanced hyperglycemia arises when this condition continues. It has become clear from large-scale clinical studies that postprandial hyperglycemia is a risk factor for arteriosclerosis independent of hypertension and hyperlipidemia [2,3]. In the STOP-NIDDM trial [4] it was shown that improvement in postprandial hyperglycemia exerted by α-glucosidase inhibitors in patients with impaired glucose tolerance (IGT) delays the onset of cardiovascular events, and the importance of correction of postprandial hyperglycemia on limiting the progression of diabetes as well as preventing the onset of macrovascular diseases was thus suggested.At present, sulfonylurea (SU) agents and rapid-and short-acting insulinotropic SU receptor (SUR) ligands are used to supplement insufficient insulin secretion in type 2 diabetic patients. SU agents have strong hypoglycemic actions, but are ineffective at promoting additional secretion of insulin after meals. In addition, these agents are known to induce protracted hypoglycemia and obesity is a problem associated with their use. Mitiglinide is a new rapid-and short-acting insulinotropic SUR ligand, a benzylsuccinic acid deriva- Study designThis was an open label study that consisted of a pretreatment observation period lasting 4 weeks and a 52-we...

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Section: Discussionsupporting

confidence: 63%

Effect of Mitiglinide on Glycemic Control over 52 Weeks in Japanese Type 2 Diabetic Patients Insufficiently Controlled with Pioglitazone Monotherapy

et al. 2009

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“…This rise was dependent upon oxidative mechanisms, as concomitant infusion of glutathione as a reducing agent abolished the effect [11]. In further support of these data, agents that increase insulin secretion and decrease postprandial glycaemia, such as mitiglinide, blunt the increase both in oxidative stress and inflammatory markers [12]. Similar results were obtained upon a glucose challenge in vivo or in vitro, which up-regulated inflammatory genes [intercellular adhesion molecule (ICAM)-1, TNF-a, IL-6], especially in subjects with the metabolic syndrome [13].…”

Section: Fasting/feeding Statementioning

confidence: 58%

Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society

Mallone

Mannering

Brooks-Worrell

et al. 2010

Clinical and Experimental Immunology

220

200

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Summary Autoimmune T cell responses directed against insulin‐producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D ‘immune staging’ and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen‐specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials.

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“…The unfavourable postprandial effects on inflammation and endothelial cell function can be attenuated by hypoglycaemic agents, e.g. mitiglinide [20], glibenclamide [18], acarbose [21] or by the antioxidant glutathione [13,14]. In these studies, the hypoglycaemic agent was compared with placebo, and different treatment regimens have not been compared.…”

mentioning

confidence: 99%

Effects of Mealtime Insulin Aspart and Bedtime NPH Insulin on Postprandial Inflammation and Endothelial Cell Function in Patients with Type 2 Diabetes

Bladbjerg

Henriksen

Akram

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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Acute hyperglycaemia exerts deleterious effects on the arterial wall. We suggested that rapid-acting insulin has a beneficial postprandial effect on endothelial dysfunction and inflammation compared with intermediate-acting insulin because of its ability to lower postprandial hyperglycaemia. This was tested in a parallel, controlled study on well-controlled patients with type 2 diabetes randomly assigned to bedtime Neutral Protamine Hagedorn (NPH) insulin (n = 41) or mealtime insulin aspart (n = 37). They were served standard diabetic meals for breakfast (8.00) and lunch (12.00). Blood samples were collected at 7.40 (fasting), 9.30, 11.30, 13.30 and 15.30 and analysed for glucose, insulin, lipids, intercellular adhesion molecules (ICAM), C-reactive protein (CRP), von Willebrand factor (vWF) and fibrinogen. The postprandial glucose response differed significantly between insulin regimens with a postprandial increase on NPH insulin and a decrease on insulin aspart. There was a minor but significant postprandial decrease in ICAM, CRP and vWF on both insulin regimens and a decrease in fibrinogen on NPH insulin. No insulin group differences were observed in postprandial responses for ICAM, CRP, vWF and fibrinogen. The rapid-acting insulin analogue aspart and the intermediate-acting insulin NPH had different effects on postprandial glucose response but similar postprandial effects on markers of inflammation and endothelial dysfunction.Type 2 diabetes is associated with increased risk of cardiovascular disease [1]. There is a strong relationship between postprandial hyperglycaemia and the risk of cardiovascular disease in epidemiological studies where postprandial hyperglycaemia is more important than fasting blood glucose or HbA1c as predictors [2][3][4][5]. However, this concept has recently been challenged [6,7] and is still highly debated [8,9].Experimental data indicate that acute hyperglycaemia can exert deleterious effects on the arterial wall measured as flow-mediated vasodilatation [10][11][12]. In line with this, the link between acute hyperglycaemia and inflammation and endothelial cell dysfunction has been investigated, showing an acute increase in interleukin 6 (IL-6) and tumour necrosis factor alfa (TNFa) [ [21] or by the antioxidant glutathione [13,14]. In these studies, the hypoglycaemic agent was compared with placebo, and different treatment regimens have not been compared. It is assumed that pharmacological agents directed towards postprandial hyperglycaemia will be more effective in reducing postprandial inflammation and endothelial cell dysfunction than treatment directed towards fasting hyperglycaemia.The aim of this short-term study in well-controlled patients with type 2 diabetes was to compare the acute effect of two different insulin treatment regimens on postprandial inflammation and endothelial cell function evaluated by biochemical markers. We suggested that the rapid-acting insulin analogue insulin aspart, directed towards postprandial hyperglycaemia, has a beneficial postprandi...

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Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Cited by 51 publications

References 38 publications

Effect of Mitiglinide on Glycemic Control over 52 Weeks in Japanese Type 2 Diabetic Patients Insufficiently Controlled with Pioglitazone Monotherapy

Effect of Mitiglinide on Glycemic Control over 52 Weeks in Japanese Type 2 Diabetic Patients Insufficiently Controlled with Pioglitazone Monotherapy

Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society

Effects of Mealtime Insulin Aspart and Bedtime NPH Insulin on Postprandial Inflammation and Endothelial Cell Function in Patients with Type 2 Diabetes

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