罗格列酮对2型糖尿病患者血压的影响

目的 观察胰岛素增敏剂罗格列酮治疗2型糖尿病伴高血压患者，评价其降压作用，探讨其降压机理。方法 32例2型糖尿病患者按血压分组，口服罗格列酮(文迪雅)4～8mg／d，共8w，计算胰岛素敏感指数和抵抗指数。结果 罗格列酮分别降低了两组的血压水平，胰岛素敏感指数升高，抵抗指数降低。结论 罗格列酮治疗2型糖尿病伴有高血压的患者的时候，在降低血浆胰岛素水平、改善IR的同时，能够明显降低血压。     

二甲双胍和吡格列酮对糖尿病大鼠胃组织胃促生长素表达的影响

目的 探讨2型糖尿病大鼠分别用二甲双胍和吡格列酮治疗后血浆和胃组织胃促生长素(ghrelin)水平的变化及其与胰岛素敏感性的关系.方法 38只清洁级雄性Wistar大鼠随机分为正常对照组(n＝7)、糖尿病对照组(n＝9)、二甲双胍治疗组(n＝9)、吡格列酮治疗组(n＝9).高糖高脂饮食加小剂量链脲佐菌素建立2型糖尿病大鼠模型,成模大鼠分别给予生理盐水、二甲双胍和吡格列酮干预8 w,酶联免疫法检测血浆ghrelin水平,免疫组织化学法检测胃组织中ghrelin的表达水平.结果 二甲双胍组和吡格列酮组血浆及胃组织中ghrelin水平较糖尿病对照组均显著升高(均P＜0.01).相关分析显示:糖尿病对照组、二甲双胍组及吡格列酮组血浆ghrelin与空腹胰岛素呈负相关,与胰岛素敏感性(ISI)呈正相关.结论 二甲双胍和吡格列酮可升高2型糖尿病大鼠血浆及胃组织中ghrelin水平,改善胰岛素抵抗.     

胰岛素联合罗格列酮治疗对糖尿病患者血浆醛固酮的作用

目的 通过比较糖尿病患者胰岛素联合罗格列酮治疗前后血浆醛固酮水平的变化,探讨罗格列酮导致水肿的机制.方法 2型糖尿病患者单独使用胰岛素治疗半年以上的患者随机分为两组,罗格列酮联合胰岛素治疗组在目前胰岛素治疗基础上加用罗格列酮4mg/日(n=10),胰岛素组继续胰岛素治疗(n=10).分别于治疗前、治疗后2、4、6个月测定立位血浆醛固酮水平,监测患者水肿情况及体重.结果 罗格列酮可以导致水肿、体重增加.罗格列酮联合胰岛素治疗组血浆醛固酮水平2个月时较对照组有升高的趋势(P＞0.05);治疗4个月时显著高于对照组(P＜0.05);至6个月时罗格列酮联合胰岛素治疗组血浆醛固酮水平较前下降,与胰岛素组无统计学差异(P＞0.05).结论 罗格列酮治疗早期出现的水肿可能与血浆醛固酮水平升高有关.     

从2型糖尿病的自然病程看治疗策略

学术研讨会纪要　　随着人们对作为 2型糖尿病重要发病机制的胰岛素抵抗的进一步深入研究 ,及新一代治疗胰岛素抵抗药物———噻唑烷二酮类药物的问世与应用 ,针对胰岛素抵抗的治疗在新世纪已成为热点问题。2 0 0 2年 2月 9日在上海波特曼酒店召开了以“马来酸罗格列酮在 2型糖尿病中的治疗地位”为主要内容的专家研讨会。研讨会上全国著名的医学专家围绕会议主题 ,结合国内外的最新研究进展和专家们自己的工作进行了精彩的讲演与热烈的讨论     

胰岛素泵联合罗格列酮钠强化治疗2型糖尿病的临床探讨

目的采用胰岛素泵（CSⅡ）联合罗格列酮钠强化治疗2型糖尿病,评价其临床疗效。方法将75例2型糖尿病患者随机分为胰岛索泵联合罗格列酮钠治疗（CSⅡ＋罗格列酮钠）组22例,单纯胰岛素泵治疗（CSⅡ）组20例、多次皮下注射胰岛素治疗（MDI）组33例,均连续治疗2周。比较三组治疗前后体重、血糖、糖化血红蛋白、空腹胰岛素、C肽、胰岛素用量、血糖达标时间、低血糖发生率及胰岛素抵抗指数（HOMA—IR）、胰岛素敏感指数（1AI）。结果胰岛素泵联合罗格列酮钠治疗组胰岛素用量最少,HOMA-IR降低最明显,IAI明显增加,低血糖发生率低,体重增加不明显。结论胰岛素泵联合罗格列酮钠强化治疗2型糖尿病,在有效控制血糖的同时节约胰岛素用量,减轻胰岛素抵抗。     

胰岛素联合罗格列酮治疗初发2型糖尿病的探讨

对42例新诊断2型糖尿病患者进行为期4周的胰岛素联合罗格列酮强化治疗,结果治疗后血糖达标时间更短,胰岛素用量更少,胰岛素抵抗指数（HomaIR）下降更明显（P〈0．01）。结论对初诊的2型糖尿病患者采用胰岛素联合罗格列酮强化治疗效果优于单纯胰岛素强化治疗。     

胰岛素和二甲双胍对2型糖尿病大鼠胃促生长素和胰岛素敏感性的影响

采用高糖高脂饮食加小剂量链脲佐菌素建立2型糖尿病(T2DM)大鼠模型,将成模大鼠随机分为T2DM对照组、胰岛素治疗组(INS组)和二甲双胍治疗组(MET组),干预治疗8周,用酶联免疫吸附法检测血浆胃促生长素.结果显示,与T2DM对照组比较,INS组胃促生长素升高而无统计学差异,MET组显著升高(P<0.01).相关分析显示,T2DM对照组、MET组胃促生长素与空腹胰岛素(FINS)呈负相关(r分别为-0.427、-0.265,P<0.05),与胰岛素敏感指数(ISI)呈正相关(r分别为0.392、0.563,P<0.05);多元线性回归分析表明,FINS、ISI与胃促生长素独立相关.提示MET可升高T2DM大鼠的血浆胃促生长素水平,提高其胰岛素敏感性.     

糖尿病伴颈动脉粥样硬化Hs-CRP水平及罗格列酮疗效探讨

目的:探讨超敏c反应蛋白(Hs-CRP)、颈动脉内膜中层厚度(IMT)、胰岛素抵抗指数(HOMA-IR)之间的关系及罗格列酮对Hs-CRP水平,颈动脉内膜中层厚度疗效。方法:将2型糖尿病患者分为2组:2型糖尿病伴颈动脉硬化组、单纯2型糖尿病组,并测定超敏反应蛋白、颈动脉内膜中层厚度,血糖、胰岛素等。结果:2型糖尿病伴颈动脉硬化组的Hs-CRP明显高于单纯2型糖尿病组,对2型糖尿病患者进行线性相关分析表明2型糖尿病患者hs-CRP与胰岛素抵抗指数、糖化血红蛋白、颈动脉IMT都有极显著的相关性(P<0.01)。与对照组相比,罗格列酮治疗组治疗后HOMA-IR、Hs-CRP、颈动脉颈IMT值明显下降(P<0.05)。结论:hs-CRP不仅与2型糖尿病相关,而且与胰岛素抵抗及颈动脉硬化有密切的关联。而罗格列酮可以降低hs-CRP的水平,改善2型糖尿病患者大血管并发症。     

罗格列酮对2型糖尿病患者血清IL-6及CRP表达的影响

2003年2月至2003年10月，我们检测了40例2型糖尿病患者罗格列酮治疗前后血清白介素6(IL-6)及C反应蛋白(CPR)水平，探讨罗格列酮改善糖代谢、胰岛素抵抗，保护胰岛素β细胞功能及抗动脉粥样硬化的作用。     

糖尿病伴径动脉粥祥硬化Hs-CRP水平及罗格列酮疗效探讨

目的:探讨超敏c反应蛋白(Hs-CRP)、颈动脉内膜中层厚度(IMT)、胰岛素抵抗指数(HOMA-IR)之间的关系及罗格列酮对H,CRP水平,颈动脉内膜中层厚度疗效.方法:将2型糖尿病患者分为2组:2型糖尿扁伴颈动脉硬化组、单纯2型糖尿病组,并测定超敏反应蛋白、颈动脉内膜中层厚度,血糖、胰岛素等.结果:2型糖尿病伴颈动脉硬化组的Hs-CRP明显高于单纯2型糖尿病组,对2型糖尿病患者进行线性相关分析表明2型糖尿病患者hg.CRP与胰岛素抵抗指数、糖化血红蛋白、颈动脉IMT都有极显著的相关性(P相似文献   

Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus

OBJECTIVE: To investigate the relationship between the circulating level of active ghrelin and abdominal adiposity, serum levels of insulin or insulin resistance in patients with type 2 diabetes mellitus. DESIGN: We measured the plasma levels of the active form of ghrelin in 18 obese and 18 nonobese patients with type 2 diabetes mellitus using a radioimmunoassay (RIA) kit. Body fat accumulation was measured by computed tomography (CT) and insulin resistance by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study. RESULTS: Plasma levels of ghrelin in obese patients with type 2 diabetes mellitus were significantly decreased compared with nonobese patients. There were significant correlations between the plasma levels of ghrelin and BMI (r=-0.505, P<0.01), visceral (r=-0.444, P<0.01), subcutaneous (r=-0.506, P<0.01) and total (r=-0.534, P<0.01) fat area, serum levels of insulin (r=-0.513, P<0.01) or GIR (r=0.478, P<0.01) in type 2 diabetic patients. The plasma level of ghrelin was significantly associated with serum levels of insulin (F=8.468, P<0.05) or GIR (F=8.522, P<0.05) after adjustment for BMI in patients with type 2 diabetes mellitus. CONCLUSIONS: Decreased plasma levels of active ghrelin are significantly associated with abdominal adiposity, hyperinsulinemia and insulin resistance in type 2 diabetic patients. Hyperinsulinemia associated with insulin resistance may suppress plasma levels of active ghrelin in patients with type 2 diabetes mellitus.     

Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion.

Ghrelin, a novel GH-releasing peptide isolated from human and rat stomach, stimulates food intake and GH secretion. We determined plasma ghrelin concentrations in patients with simple obesity, anorexia nervosa, and type 2 diabetes mellitus by RIA. We also studied plasma ghrelin responses to glucose load and meal intake and obtained a 24-h profile of circulating ghrelin in humans. Plasma ghrelin concentrations in patients with simple obesity and anorexia nervosa were lower and higher, respectively, than those of healthy subjects with normal body weight. Among those with type 2 diabetes mellitus, obese patients had lower and lean patients higher fasting plasma ghrelin concentrations than normal-weight patients. Fasting plasma ghrelin concentration was negatively correlated with body mass index in both nondiabetic and diabetic patients. Plasma ghrelin concentrations of normal subjects decreased significantly after oral and iv glucose administration; a similar response was also observed in diabetic patients after a meal tolerance test, reaching a nadir of 69% of the basal level after the meal. Circulating plasma ghrelin showed a diurnal pattern with preprandial increases, postprandial decreases, and a maximum peak at 0200 h. This study demonstrates that nutritional state is a determinant of plasma ghrelin in humans. Ghrelin secretion is up-regulated under conditions of negative energy balance and down-regulated in the setting of positive energy balance. These findings suggest the involvement of ghrelin in the regulation of feeding behavior and energy homeostasis.     

2型糖尿病患者外源性给予胰升血糖素对肥胖与血浆Ghrelin的影响

目的探讨肥胖及非肥胖2型糖尿病（T2DM）患者胰岛素抵抗（IR）与生长激素释放肽Gh—relin分泌的关系。方法肥胖T2DM患者26例（Ob＋T2DM组）及非肥胖T2DM患者32例（NOb＋T2DM组）,正常对照30名（NC组）行胰升血糖素－C-P释放试验,同步取血测定血浆Ghrelin和C-P。结果（1）Ob4-T2DM组空腹Ghrelin水平低于NC组和NOb＋T2DM组（P〈0．05或P〈0．01）;Ob＋T2DM组FC-P及胰岛素抵抗指数（HOMA2-IR）高于NC组和NOb＋T2DM组（P〈0．01或P〈0．05）。静脉推注胰升血糖素后,NC组Ghrdin水平显著下降（P〈0．01）,肥胖及非肥胖T2DM组Ghrelin水平无显著性改变。（2）Pearson相关分析显示空腹血浆Ghrelin水平分别与WC、BMI、体脂百分比、体脂重量呈负相关;多元回归分析显示腰围（WC）是Ghrelin水平的负性预测因子（回归方程Y=4．814—0．0265X）。（3）Ob＋T2DM组中,空腹血浆Ghrelin水平分别与WC、BMI、体脂百分比、体脂重量、HOMA2-IR呈负相关。结论外源性给予胰升血糖素对T2DM患者Ghrelin抑制效应减弱;肥胖T2DM患者血浆Ghrelin水平较非肥胖患者明显降低,且与WC、BMI、体脂百分比、体脂重量、HOMA2-IR负相关;中心性肥胖T2DM患者血浆Ghrelin水平下降与IR有关。     

2型糖尿病患者应用二甲双胍治疗前后血浆胃促生长素及YY肽水平

目的 观察二甲双胍治疗对新诊断2型糖尿病患者血浆胃促生长素、YY肽(PYY)水平的影响,探讨二甲双胍对2型糖尿病患者体重影响个体差异性的机制.方法 采用前瞻性巢式病例对照研究作为研究设计方案.64例新诊断2型糖尿病患者应用二甲双胍治疗12周,根据治疗后体重的变化情况,分为体重减轻组及体重未减轻组,治疗前后测定空腹血浆胃促生长素、PYY水平及相关代谢指标.结果 2型糖尿病患者经二甲双胍治疗后空腹血浆胃促生长素水平均较治疗前明显下降[(10.71 +2.68对11.81±3.19)ng/ml,P＜0.05],空腹血浆PYY水平均较治疗前明显升高[(136.86±39.14对128.42±37.31)pg/ml,P＜0.05].治疗后有43.7％的2型糖尿病患者出现体重明显下降.体重减轻组在治疗后空腹血浆胃促生长素水平下降16.6％,降幅高于体重未减轻组的6.2％(P＜0.05);体重减轻组在治疗后空腹血浆PYY水平升高10.8％,升幅高于体重未减轻组的3.5％(P＜0.05).结论 2型糖尿病患者二甲双胍治疗后体重明显减轻者较体重基本保持不变者,空腹血浆胃促生长素水平降低更显著,空腹血浆PYY水平升高更显著,具体机制还有待进一步研究.     

2型糖尿病患者应用甘精胰岛素治疗前后内脏脂肪素水平的变化

目的探讨应用甘精胰岛素治疗的2型糖尿病患者血浆内脏脂肪素（Visfatin）水平的变化与胰岛素抵抗及血糖的关系。方法共32例2型糖尿病患者,比较其治疗前后空腹（FPG）及餐后血糖（2hPG）、甘油三酯（TG）、糖化血红蛋白（HbA1c）、空腹胰岛素（Fins）、胰岛素抵抗指数（HOMA-IR）、胰岛素分泌指数（HOMA-β）、Visfatin等相关指标。同时选择性别、年龄等相匹配的26名健康体检者作为对照组进行比较。结果32例糖尿病患者治疗前后的TG、FPG、2hPG、HbA]C、HOMA-IR、HOMA-13差异有统计学意义（P〈0．05）,治疗后Visfatin水平降低（P〈0．05）,与健康人相比,糖尿病患者Visfatin水平降低（Pd0．01）;Pearson相关分析显示Visfatin与HbA1C、Fins、HOMA-IR呈正相关（r=0．259,Pd0．05;r=0．586,P〈0．01;r=0．385,P〈0．01）。多元线性逐步回归分析表明HOMA-IR是血浆Vis—fatin的独立相关因素。结论2型糖尿病患者血浆Visfatin水平的变化与胰岛素抵抗及平均血糖有关,可能在糖尿病及胰岛素抵抗的发病机制中具有一定的作用。     

不同甲状腺功能状态血清胃促生长素水平的变化

探讨不同甲状腺功能状态下血清胃促生长素水平的变化及其与体重指数、腰臀比、甲状腺功能、血糖、胰岛素及胰岛素抵抗的关系.初诊甲状腺功能亢进症(甲亢)患者50例及甲状腺功能减退症(甲减)患者30例,测定其治疗前及甲状腺功能恢复正常后空腹血清胃促生长素、胰岛紊、血糖、游离三碘甲状腺原氨酸(FT_3)、游离甲状腺素(FT_4)和促甲状腺激素(TSH)水平,同时测量身高、体重、腰围、臀围,计算体重指数、腰臀比、稳态模型评估的胰岛素抵抗指数(HOMA-IR)等,以健康对照者30例为对照.甲亢患者治疗前血清胃促生长素水平低于正常对照组[(63.2±9.6)ng/L对(80.9±13.9)ng/L,P<0.01],经多元逐步回归分析提示HOMA-IR是胃促生长素的独立影响因素(r=-0.314,P=0.027).甲状腺功能减退症患者,治疗前后胃促生长素水平和正常对照组比较均无明显差异(均P0.05).本研究提示,在不同甲状腺功能状态下,胰岛素抵抗可能是胃促生长素水平改变的重要影响因素.     

Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans

CONTEXT: Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. OBJECTIVE: The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. DESIGN AND PATIENTS: The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed. RESULTS: Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). CONCLUSION: The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.     

Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy

The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P < 0.0001); ghrelin levels on octreotide ranged between 26% and 70% of baseline levels. Serum ghrelin levels were suppressed significantly during the oral glucose tolerance test in both groups. Pretherapy ghrelin levels correlated negatively with serum insulin levels (r = -0.494; P = 0.03) and insulin resistance as estimated by the homeostasis model assessment score (r = -0.573; P = 0.01). In patients without diabetes mellitus, serum insulin levels in the surgical group were 19.7 +/- 5.4 microU/ml before surgery and fell to 9.7 +/- 0.93 microU/ml after surgery (P = 0.05); levels in the octreotide group were 13.9 +/- 2.8 microU/ml before and fell to 11.2 +/- 2.8 microU/ml on octreotide (P = 0.03). Pretherapy ghrelin levels did not correlate with weight or body mass index, but after therapy in the surgery group ghrelin correlated negatively with weight (r = -0.823, P = 0.012) as has been demonstrated by others in healthy subjects. Ghrelin secretion is dysregulated in active acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with the postsurgery normalization of GH and IGF-I and improved insulin resistance. In contrast to surgical therapy, long-acting octreotide therapy persistently suppressed serum ghrelin levels. It remains to be determined whether altered circulating ghrelin concentrations could impact on body composition changes in acromegaly.     

Testosterone replacement therapy restores normal ghrelin in hypogonadal men

We recently described a connection between androgens and ghrelin in women affected by the polycystic ovary syndrome. To further investigate the interaction between sex steroids and ghrelin, we investigated circulating ghrelin levels in a group of hypogonadal men before and after therapeutic intervention aiming at normalization low testosterone (T) concentrations. Seven hypogonadal men were compared with nine overweight/moderately obese men matched for body mass index and body fat distribution parameters, as well as with 10 normal weight controls. Total and free T and plasma ghrelin levels were significantly lower in the hypogonadal men than in the control groups. Hypogonadal men also had a significantly higher insulin resistance state. Ghrelin levels were positively correlated with both total and free T concentrations. A significant correlation was also found between ghrelin and the anthropometric parameters and the insulin resistance indexes. However, in a multiple regression analysis in which a correction for all covariants was performed, only the relationship with total and free T persisted. After the 6-month replacement T therapy, ghrelin levels of hypogonadal patients increased and did not differ significantly in comparison with both control groups. The positive correlation between ghrelin and androgens still persisted after T replacement therapy, after adjusting for confounding variables. These data further indicate that sex hormones modulate circulating ghrelin concentrations in humans. This may be consistent with the concept that ghrelin may exert a relevant role in the endocrine network connecting the control of the reproductive system with the regulation of energy balance.     

Role of ghrelin in streptozotocin-induced diabetic hyperphagia

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from the rat stomach. We have previously reported that central administration of ghrelin increases food intake and body weight. To investigate the role of ghrelin in the hyperphagic response to uncontrolled diabetes, adult male rats were studied 14 days after administration of streptozotocin (STZ) or vehicle. STZ-treated diabetic rats were markedly hyperphagic. This hyperphagia was accompanied by hyperglycemia, hypoinsulinemia, and reduced plasma GH levels. Treatment of diabetic rats with insulin reversed these changes. Plasma ghrelin concentrations in untreated diabetic rats were significantly higher than in control rats and were normalized by insulin treatment. The ghrelin gene expression in the stomach was also higher in STZ diabetic rats than in control rats, but this difference was not significant. In contrast, plasma leptin was markedly reduced in STZ diabetic rats. This reduction in plasma leptin levels was reversed by insulin treatment. In addition, hypothalamic NPY mRNA levels were increased in STZ-treated diabetic rats and were reversed by insulin treatment. Furthermore, the hyperphagia was partially reversed by the administration of a ghrelin-receptor antagonist. Therefore, we conclude that the elevated plasma ghrelin levels, along with decreased plasma leptin levels, could contribute to the diabetic hyperphagia in part by increasing hypothalamic NPY. This is the first report to show the pathophysiological significance of ghrelin in diabetes.