Mitra Zarifkar, Sina Noshad, Mona Shahriari, Mohsen Afarideh, Elias Khajeh, Zahra Karimi, Alireza Ghajar, Alireza Esteghamati
{"title":"外周Orexin-A与2型糖尿病胰岛素抵抗的负相关:一项随机临床试验","authors":"Mitra Zarifkar, Sina Noshad, Mona Shahriari, Mohsen Afarideh, Elias Khajeh, Zahra Karimi, Alireza Ghajar, Alireza Esteghamati","doi":"10.1900/RDS.2017.14.301","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus, and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months.</p><p><strong>Methods: </strong>This study was designed as a randomized, open-label, clinical trial. Before allocation, sixty medication-naïve, newly-diagnosed, type 2 diabetes patients underwent a 75 g oral glucose tolerance test (OGTT). Afterwards, using a randomized trial design (IRCT201102275917N1) patients were allocated to either the metformin (1000 mg daily) or pioglitazone (30 mg daily) arm, and were reexamined after three months. Serum insulin, plasma glucose, and orexin concentrations were measured at baseline, during OGTT, and after three months.</p><p><strong>Results: </strong>Orexin concentrations significantly decreased after OGTT (0 vs. 120 min: 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml, p < 0.001). Insulin resistance determined by homeostasis model assessment of insulin resistance (HOMA-IR) was significantly and negatively correlated with orexin (r = -0.301, p = 0.024). Furthermore, orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT (r = 0.326, p = 0.014). Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively. Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different (p = 0.742).</p><p><strong>Conclusions: </strong>There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients. Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control.</p>","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115012/pdf/RevDiabeticStud-14-301.pdf","citationCount":"10","resultStr":"{\"title\":\"Inverse Association of Peripheral Orexin-A with Insulin Resistance in Type 2 Diabetes Mellitus: A Randomized Clinical Trial.\",\"authors\":\"Mitra Zarifkar, Sina Noshad, Mona Shahriari, Mohsen Afarideh, Elias Khajeh, Zahra Karimi, Alireza Ghajar, Alireza Esteghamati\",\"doi\":\"10.1900/RDS.2017.14.301\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus, and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months.</p><p><strong>Methods: </strong>This study was designed as a randomized, open-label, clinical trial. Before allocation, sixty medication-naïve, newly-diagnosed, type 2 diabetes patients underwent a 75 g oral glucose tolerance test (OGTT). Afterwards, using a randomized trial design (IRCT201102275917N1) patients were allocated to either the metformin (1000 mg daily) or pioglitazone (30 mg daily) arm, and were reexamined after three months. Serum insulin, plasma glucose, and orexin concentrations were measured at baseline, during OGTT, and after three months.</p><p><strong>Results: </strong>Orexin concentrations significantly decreased after OGTT (0 vs. 120 min: 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml, p < 0.001). Insulin resistance determined by homeostasis model assessment of insulin resistance (HOMA-IR) was significantly and negatively correlated with orexin (r = -0.301, p = 0.024). Furthermore, orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT (r = 0.326, p = 0.014). Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively. Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different (p = 0.742).</p><p><strong>Conclusions: </strong>There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients. 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引用次数: 10
摘要
目的:探讨2型糖尿病患者血清促食欲素浓度与胰岛素抵抗/敏感性的关系,并研究抗高血糖治疗3个月后对促食欲素浓度的影响。方法:本研究设计为随机、开放标签的临床试验。在分配之前,60例medication-naïve新诊断的2型糖尿病患者进行了75 g口服葡萄糖耐量试验(OGTT)。随后,采用随机试验设计(IRCT201102275917N1),将患者分配到二甲双胍(每天1000 mg)或吡格列酮(每天30 mg)组,并在3个月后重新检查。在基线、OGTT期间和三个月后测量血清胰岛素、血浆葡萄糖和食欲素浓度。结果:OGTT后食欲素浓度显著降低(0 vs. 120min; 0.63±0.07 vs. 0.31±0.03 ng/ml, p < 0.001)。胰岛素抵抗的稳态模型评估(HOMA-IR)与食欲素呈显著负相关(r = -0.301, p = 0.024)。此外,食欲素浓度与OGTT得出的胰岛素敏感性指数呈显著正相关(r = 0.326, p = 0.014)。二甲双胍和吡格列酮治疗3个月后,胰岛素敏感性和促食欲素浓度分别显著提高26% (p = 0.025)和14% (p = 0.076)。组间分析显示,二甲双胍与吡格列酮对食欲素浓度的影响无显著性差异(p = 0.742)。结论:2型糖尿病患者外周食欲素浓度与胰岛素抵抗呈负相关。按比例使用二甲双胍或吡格列酮进行三个月的抗高血糖治疗,可通过改善胰岛素抵抗和改善血糖控制来增加食欲素浓度。
Inverse Association of Peripheral Orexin-A with Insulin Resistance in Type 2 Diabetes Mellitus: A Randomized Clinical Trial.
Aims: To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus, and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months.
Methods: This study was designed as a randomized, open-label, clinical trial. Before allocation, sixty medication-naïve, newly-diagnosed, type 2 diabetes patients underwent a 75 g oral glucose tolerance test (OGTT). Afterwards, using a randomized trial design (IRCT201102275917N1) patients were allocated to either the metformin (1000 mg daily) or pioglitazone (30 mg daily) arm, and were reexamined after three months. Serum insulin, plasma glucose, and orexin concentrations were measured at baseline, during OGTT, and after three months.
Results: Orexin concentrations significantly decreased after OGTT (0 vs. 120 min: 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml, p < 0.001). Insulin resistance determined by homeostasis model assessment of insulin resistance (HOMA-IR) was significantly and negatively correlated with orexin (r = -0.301, p = 0.024). Furthermore, orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT (r = 0.326, p = 0.014). Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively. Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different (p = 0.742).
Conclusions: There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients. Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control.
期刊介绍:
The Review of Diabetic Studies (RDS) is the society"s peer-reviewed journal published quarterly. The purpose of The RDS is to support and encourage research in biomedical diabetes-related science including areas such as endocrinology, immunology, epidemiology, genetics, cell-based research, developmental research, bioengineering and disease management.